# NM_139276.3(STAT3):c.711C>T (p.Asp237=)

https://sugi.bio/variant/stat3-p-asp237

## Summary

**STAT3 p.Asp237= (c.711C>T)** is classified **Benign** in STAT3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). Low-frequency (popmax 2.17%, afr); Associated with hyper-IgE recurrent infection syndrome 1, autosomal dominant.

**At a glance:** Benign · review: Multiple submitters · rsID rs17882069 · 6 submitters · 1 linked condition · low-frequency (popmax 2.17%, afr)

> **Built without this gene's context.** ClinVar files this variant under an overlapping gene, so its own gene's record set does not contain it and this page is assembled from the variant alone. Gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up — absent from this page, not from the data.

## For patients & families {#patients}

This is a change in the STAT3 gene that is classified as benign — not considered disease-causing, submitted by 6 submitters, and is linked to hyper-IgE recurrent infection syndrome 1, autosomal dominant.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal dominant |
| Age of onset (of this condition) | Infancy, Neonatal |
| Prevalence | 1-9 / 1 000 000 (Europe) |
| Clinical trials | 8 registered for this condition — see ClinicalTrials.gov |

**Commonly reported features of Autosomal dominant hyper-IgE syndrome due to STAT3 deficiency** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Eczematoid dermatitis — Very frequent (99-80%)
- Skin rash — Very frequent (99-80%)
- Pruritus — Very frequent (99-80%)
- Recurrent respiratory infections — Very frequent (99-80%)
- Recurrent infections — Very frequent (99-80%)
- Increased circulating IgE level — Very frequent (99-80%)
- Generalized abnormality of skin — Very frequent (99-80%)
- Atelectasis — Very frequent (99-80%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0006800/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [STAT3](https://sugi.bio/atlas/gene/STAT3/) |
| Protein change (HGVS p.) | p.Asp237= |
| Coding change (HGVS c.) | c.711C>T |
| MANE Select transcript | [NM_139276](https://www.ncbi.nlm.nih.gov/nuccore/NM_139276) |
| dbSNP | [rs17882069](https://www.ncbi.nlm.nih.gov/snp/rs17882069/) |
| Variant type | single nucleotide variant |
| Location | chr17:42337521-42337521 (GRCh38) |
| ClinVar | [VCV36793](https://www.ncbi.nlm.nih.gov/clinvar/variation/36793/) |

**All HGVS expressions:** `LRG_112:g.55975C>T`, `LRG_112t1:c.711C>T`, `NC_000017.10:g.40489539G>A`, `NC_000017.11:g.42337521G>A`, `NG_007370.1:g.55975C>T`, `NM_001369512.1:c.711C>T`, `NM_001369513.1:c.711C>T`, `NM_001369514.1:c.711C>T`, `NM_001369516.1:c.711C>T`, `NM_001369517.1:c.711C>T`, `NM_001369518.1:c.711C>T`, `NM_001369519.1:c.711C>T`, `NM_001369520.1:c.711C>T`, `NM_001384984.1:c.711C>T`, `NM_001384985.1:c.633C>T`, `NM_001384986.1:c.711C>T`, `NM_001384987.1:c.711C>T`, `NM_001384988.1:c.711C>T`, `NM_001384989.1:c.615C>T`, `NM_001384990.1:c.711C>T`, `NM_001384991.1:c.711C>T`, `NM_001384992.1:c.711C>T`, `NM_001384993.1:c.711C>T`, `NM_003150.4:c.711C>T`, `NM_139276.3:c.711C>T`, `NM_213662.2:c.711C>T`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP -5.674, GERP -3.73 — fast-evolving / accelerated position
- CADD: **PHRED 0.91**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **not looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency (gnomAD v4.1): grpmax **2.17%** (afr) · FAF95 2.08% · FAF99 2.05% · 1,627/75,008 in the highest group · 1,878/1,614,138 alleles overall — low-frequency (popmax 2.17%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 2.17% | 46 |
| Admixed American | 0.158% | 632 |
| Remaining individuals (not grpmax-eligible) | 0.133% | 753 |
| Middle Eastern | 0.0495% | 2,021 |
| European (non-Finnish) | 0.00568% | 17,612 |
| South Asian | 0.00329% | 30,361 |

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Clinical significance {#significance}

**Benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2026-01-27.

**Submitter consensus:** unanimous (6/6 Benign).

**Submission history:** 5 submissions (2011–2026); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| GeneDx | Benign | criteria provided, single submitter | clinical testing | 2015-03-03 |
| Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Benign | criteria provided, single submitter | curation | 2011-08-18 |
| Mayo Clinic Laboratories, Mayo Clinic | Benign | criteria provided, single submitter | clinical testing | 2021-02-02 |
| Breakthrough Genomics, Breakthrough Genomics | Benign | criteria provided, single submitter | not provided |  |
| PreventionGenetics, part of Exact Sciences | Benign | no assertion criteria provided | clinical testing | 2019-03-29 |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2026-01-27 |

## Associated conditions {#conditions}

[hyper-IgE recurrent infection syndrome 1, autosomal dominant](https://sugi.bio/atlas/disease/hyper-ige-recurrent-infection-syndrome-1-autosomal-dominant/).

**Reported phenotype names (ClinVar):** Hyper-IgE recurrent infection syndrome 1, autosomal dominant, STAT3 gain of function, not provided, STAT3-related disorder, not specified, STAT3-related condition, JOB SYNDROME, Job's Syndrome, Hyper-IgE recurrent infection syndrome 1, STAT3 Hyper IgE Syndrome.

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 36793). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*