SRRM2 p.Pro477=
c.1431C>T · VCV4928165
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.662%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.84 | GERP 0.36, phastCons 1 |
| Overall | ||
| CADD | 2.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.662%
East Asian · 297/44,880 alleles
Filtering AF
0.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.576%
Overall
0.024%
387/1,614,108 alleles · rare
exomes 350/1,461,836 · genomes 37/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.662% | 151 |
| South Asian | 0.0417% | 2,397 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,167 |
| Middle Eastern | 0.0165% | 6,062 |
| European (non-Finnish) | 0.00305% | 32,778 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- SRRM2
- Protein
- p.Pro477=
- Coding
- c.1431C>T
- MANE Select
- NM_016333
- Type
- single nucleotide variant
- Location
- chr16:2761959 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 477
- the 'disordered' region; a UniProt-annotated variant site (in mrd72; likely pathogenic)
Similar variants
- SRRM2 p.Arg1836Ter Pathogenic ★★ same type
- SRRM2 p.Arg1875Ter Pathogenic/Likely pathogenic ★★ same type
- SRRM2 p.Arg280Ter Pathogenic ★★ same type
- SRRM2 p.Arg628Ter Pathogenic ★★ same type
- SRRM2 p.Ala2245Val Uncertain significance ★★ same type
- SRRM2 p.Arg1213Gly Uncertain significance ★★ ⚠ same type
- SRRM2 p.Arg1723Lys Uncertain significance ★★ ⚠ same type
- SRRM2 p.Arg1971Gln Uncertain significance ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/srrm2-p-pro477 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown