# NM_153614.4(DNAJB13):c.882C>T (p.Phe294=)

https://sugi.bio/variant/dnajb13-p-phe294

## Summary

**DNAJB13 p.Phe294= (c.882C>T)** is classified **Benign** in DNAJB13 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 36.7%, amr) — too common for a highly-penetrant pathogenic allele.

**At a glance:** Benign · review: Multiple submitters · rsID rs2306819 · 4 submitters · common (popmax 36.7%, amr) — too common for a highly-penetrant pathogenic allele

## For patients & families {#patients}

This is a change in the DNAJB13 gene that is classified as benign — not considered disease-causing, submitted by 4 submitters.

*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.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [DNAJB13](https://sugi.bio/atlas/gene/DNAJB13/) |
| Protein change (HGVS p.) | p.Phe294= |
| Coding change (HGVS c.) | c.882C>T |
| MANE Select transcript | [NM_153614](https://www.ncbi.nlm.nih.gov/nuccore/NM_153614) |
| dbSNP | [rs2306819](https://www.ncbi.nlm.nih.gov/snp/rs2306819/) |
| Variant type | single nucleotide variant |
| Location | chr11:73970045-73970045 (GRCh38) |
| ClinVar | [VCV1253105](https://www.ncbi.nlm.nih.gov/clinvar/variation/1253105/) |

**All HGVS expressions:** `NC_000011.10:g.73970045C>T`, `NC_000011.9:g.73681090C>T`, `NG_053111.1:g.24727C>T`, `NM_001377263.1:c.708C>T`, `NM_153614.4:c.882C>T`

## Computational & population evidence {#evidence}

**Concordance:** Evidence sources **disagree** — common (popmax 36.7%, amr) — too common for a highly-penetrant pathogenic allele.

- **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 -6.516, GERP -8.32 — fast-evolving / accelerated position
- CADD: **PHRED 4.299**. 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: **below the reporting threshold**. This position is scored for a different substitution (C>A, Δ0.39 acceptor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **36.7%** (amr) · FAF95 36.3% · FAF99 36.1% · 21,745/59,286 in the highest group · 464,579/1,609,274 alleles overall — common (popmax 36.7%, amr) — too common for a highly-penetrant pathogenic allele.

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Amish (not grpmax-eligible) | 37.4% | 3 |
| Admixed American (grpmax) | 36.7% | 3 |
| Middle Eastern | 32.9% | 3 |
| Finnish (not grpmax-eligible) | 30.5% | 3 |
| European (non-Finnish) | 29.7% | 3 |
| Ashkenazi Jewish (not grpmax-eligible) | 29.5% | 3 |
| Remaining individuals (not grpmax-eligible) | 28.1% | 4 |
| South Asian | 22.7% | 4 |
| African / African-American | 21.6% | 5 |
| East Asian | 17.4% | 6 |

Amish shows a higher raw frequency than the grpmax group. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and "Remaining individuals" — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

*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.*

## Gene constraint & dosage {#gene-context}

**DNAJB13** population constraint: LOEUF 0.9, pLI 0.00019212, missense-Z 0.35175. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **primary ciliary dyskinesia 34** — Moderate (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 86.81, 61% of residues very-high.

**1 experimental structure(s)** (PDB): [8J07](https://www.rcsb.org/structure/8J07).

## Clinical significance {#significance}

**Benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2026-02-04.

**Submitter consensus:** unanimous (4/4 Benign).

**Submission history:** 4 submissions (2018–2026); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| GeneDx | Benign | criteria provided, single submitter | clinical testing | 2018-11-10 |
| Breakthrough Genomics, Breakthrough Genomics | Benign | criteria provided, single submitter | not provided |  |
| Mayo Clinic Laboratories, Mayo Clinic | Benign | criteria provided, single submitter | clinical testing | 2022-04-26 |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2026-02-04 |

**Reported phenotype names (ClinVar):** not provided, not specified, AllHighlyPenetrant, none provided.

## Similar variants {#similar}

Related DNAJB13 variant pages (same residue, condition, or type): [DNAJB13 p.Gln136Ter](/variant/dnajb13-p-gln136ter), [DNAJB13 p.Arg131Gln](/variant/dnajb13-p-arg131gln), [DNAJB13 p.Arg142Gln](/variant/dnajb13-p-arg142gln), [DNAJB13 p.Arg222Cys](/variant/dnajb13-p-arg222cys), [DNAJB13 p.Arg301Cys](/variant/dnajb13-p-arg301cys), [DNAJB13 p.Asn14Asp](/variant/dnajb13-p-asn14asp), [DNAJB13 p.Asp169Gly](/variant/dnajb13-p-asp169gly), [DNAJB13 p.Asp65Asn](/variant/dnajb13-p-asp65asn).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); 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 1253105). 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.*