SRCAP p.Leu1823=
c.5469T>C · rs370111987 · VCV284335
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.201%, afr)
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 -0.64 | GERP -5.3, phastCons 0.002 |
| Overall | ||
| CADD | 4.625 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.201%
African / African-American · 151/75,044 alleles
Filtering AF
0.175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.165%
Overall
0.00997%
161/1,614,190 alleles · rare
exomes 70/1,461,894 · genomes 91/152,296 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.201% | 497 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,502 |
| Admixed American | 0.00666% | 15,006 |
| European (non-Finnish) | 8.47e-05% | 1,180,036 |
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.Leu1823=
- Coding
- c.5469T>C
- MANE Select
- NM_006662
- dbSNP
- rs370111987
- Type
- single nucleotide variant
- Location
- chr16:30724893 (GRCh38)
- Gene constraint
- LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 1823
- a UniProt-annotated variant site (in dehmba)
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-leu1823 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown