SRCAP p.Pro1610Leu
c.4829C>T · rs748074399 · VCV2716749
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2114 | likely benign |
|---|---|---|
| REVEL | 0.286 | benign-leaning |
| SaProt | — | not scored · why |
| ⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.7, phastCons 1 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic |
| Overall | ||
| CADD | 23.7 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| Admixed Americangrpmax | 0.00333% | 30,000 |
| South Asian | 0.00329% | 30,359 |
| African / African-American | 0.00267% | 37,446 |
| European (non-Finnish) | 0.00119% | 84,289 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. 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.
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.Pro1610Leu
- Coding
- c.4829C>T
- MANE Select
- NM_006662
- dbSNP
- rs748074399
- Type
- single nucleotide variant
- Location
- chr16:30724253 (GRCh38)
- Gene constraint
- LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 1610
- a UniProt-annotated variant site (in dehmba)
Similar variants
- SRCAP p.Pro1610= Likely benign ★★ same residue
- 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
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-pro1610leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown