SRCAP p.Cys141=
c.423C>T · rs755600748 · VCV1918875
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP -0.76, phastCons 1 |
| Overall | ||
| CADD | 14.23 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 4/91,084 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.00118%
19/1,614,034 alleles · very rare
exomes 17/1,461,886 · genomes 2/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,771 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| Admixed American | 0.00167% | 60,002 |
| African / African-American | 0.00133% | 74,908 |
| European (non-Finnish) | 0.000932% | 107,275 |
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
- SRCAP
- Protein
- p.Cys141=
- Coding
- c.423C>T
- MANE Select
- NM_006662
- dbSNP
- rs755600748
- Type
- single nucleotide variant
- Location
- chr16:30707299 (GRCh38)
- Gene constraint
- LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 141
- the hsa domain; an α-helix
Similar variants
- SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same type
- SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same type
- SRCAP p.Arg2444Ter Pathogenic ★★ same type
- SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same type
- SRCAP p.Arg2748Ter Pathogenic ★★ same type
- SRCAP p.Gln2407Ter Pathogenic ★★ same type
- SRCAP p.Gln2419Ter Pathogenic ★★ same type
- SRCAP p.Gln2665Ter Pathogenic/Likely pathogenic ★★ 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/srcap-p-cys141 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown