SRCAP p.Leu2817=
c.8451G>C · rs541036742 · VCV721033
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0112%, 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 5.9 | GERP -0.99, phastCons 1 |
| Overall | ||
| CADD | 2.839 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0112%
East Asian · 5/44,842 alleles
Filtering AF
0.00435%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.000436%
7/1,604,286 alleles · ultra-rare
exomes 4/1,452,052 · genomes 3/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0112% | 8,968 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,032 |
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.Leu2817=
- Coding
- c.8451G>C
- MANE Select
- NM_006662
- dbSNP
- rs541036742
- Type
- single nucleotide variant
- Location
- chr16:30738491 (GRCh38)
- Gene constraint
- LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 2817
- the 'disordered' region; a UniProt-annotated variant site (in dehmba); a UniProt-annotated variant site (in flhs)
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-leu2817 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown