SRCAP p.Arg2421=
c.7263C>A · rs74947321 · VCV160037
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.29%, 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 -0.23 | GERP 0.039, phastCons 0.24 |
| Overall | ||
| CADD | 2.901 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.29%
African / African-American · 3,215/74,990 alleles
Filtering AF
4.16%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.11%
Overall
0.237%
3,820/1,614,060 alleles · low-frequency
exomes 1,860/1,461,892 · genomes 1,960/152,168 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.29% | 23 |
| Admixed American | 0.492% | 203 |
| Middle Eastern | 0.462% | 216 |
| Remaining individualsnot grpmax-eligible | 0.322% | 311 |
| European (non-Finnish) | 0.00669% | 14,937 |
| South Asian | 0.0022% | 45,534 |
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.Arg2421=
- Coding
- c.7263C>A
- MANE Select
- NM_006662
- dbSNP
- rs74947321
- Type
- single nucleotide variant
- Location
- chr16:30737303 (GRCh38)
- Gene constraint
- LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 2421
- the 'disordered' region; a UniProt-annotated variant site (in dehmba); a UniProt-annotated variant site (in flhs)
Similar variants
- SRCAP p.Arg2421Cys Uncertain significance ★ ⚠ same residue
- SRCAP p.Arg2421His Uncertain significance ★ same residue
- SRCAP p.Arg2421Leu 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
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-arg2421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown