# NM_001083961.2(WDR62):c.3711T>C (p.Ser1237=)

https://sugi.bio/variant/wdr62-p-ser1237

## Summary

**WDR62 p.Ser1237= (c.3711T>C)** is classified **Likely benign** in WDR62 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-06). Very rare (popmax 0.00314%, nfe).

**At a glance:** Likely benign · review: Single submitter · rsID rs887740291 · 1 submitter · very rare (popmax 0.00314%, nfe)

## For patients & families {#patients}

This is a change in the WDR62 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*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 | [WDR62](https://sugi.bio/atlas/gene/WDR62/) |
| Protein change (HGVS p.) | p.Ser1237= |
| Coding change (HGVS c.) | c.3711T>C |
| MANE Select transcript | [NM_001083961](https://www.ncbi.nlm.nih.gov/nuccore/NM_001083961) |
| dbSNP | [rs887740291](https://www.ncbi.nlm.nih.gov/snp/rs887740291/) |
| Variant type | single nucleotide variant |
| Location | chr19:36103539-36103539 (GRCh38) |
| ClinVar | [VCV3014998](https://www.ncbi.nlm.nih.gov/clinvar/variation/3014998/) |

**All HGVS expressions:** `NC_000019.10:g.36103539T>C`, `NC_000019.9:g.36594441T>C`, `NG_028101.2:g.53644T>C`, `NM_001083961.2:c.3711T>C`, `NM_001411145.1:c.3696T>C`, `NM_001411146.1:c.3462T>C`, `NM_001411147.1:c.3360T>C`, `NM_173636.5:c.3696T>C`

## 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 -4.177, GERP -3.41 — fast-evolving / accelerated position
- CADD: **PHRED 0.362**. 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 (T>G, Δ0.22 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 **0.00314%** (nfe) · FAF95 0.00231% · FAF99 0.00202% · 37/1,180,000 in the highest group · 37/1,614,000 alleles overall — very rare (popmax 0.00314%, nfe).

*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}

**WDR62** population constraint: LOEUF 0.806, pLI 1.0718e-25, missense-Z 1.767; ClinGen dosage — haploinsufficiency gene assoc. with recessive phenotype, triplosensitivity Not yet evaluated/3. *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):

- **microcephaly 2, primary, autosomal recessive, with or without cortical malformations** — Definitive (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 61.19, 35% of residues very-high.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2025-02-06.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2025-02-06 |

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

## Same-residue context {#hotspot}

Residue **1237** carries **1 other pathogenic ClinVar variant** — a recurrently-mutated position: [WDR62 p.Ser1237fs](/variant/wdr62-p-ser1237fs). *Positional co-occurrence of independent ClinVar records, not functional proof.*

## Similar variants {#similar}

Related WDR62 variant pages (same residue, condition, or type): [WDR62 p.Ser1237fs](/variant/wdr62-p-ser1237fs), [WDR62 c.1234-1G>A](/variant/wdr62-c-1234-minus-1g-a), [WDR62 c.177+1G>C](/variant/wdr62-c-177-plus-1g-c), [WDR62 c.2333+2T>C](/variant/wdr62-c-2333-plus-2t-c), [WDR62 c.2520+5G>T](/variant/wdr62-c-2520-plus-5g-t), [WDR62 c.269+1G>T](/variant/wdr62-c-269-plus-1g-t), [WDR62 c.3462+1G>A](/variant/wdr62-c-3462-plus-1g-a), [WDR62 c.3462+1G>C](/variant/wdr62-c-3462-plus-1g-c).

### 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 3014998). 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.*