SRCAP p.Gln450=
c.1350G>A · rs146916680 · VCV916312
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0506%, mid)
Conditions
2
developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities
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 0.26 | GERP -2, phastCons 0.94 |
| Overall | ||
| CADD | 5.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0506%
Middle Eastern · 3/5,932 alleles
Filtering AF
0.0137%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00733%
Overall
0.00535%
86/1,606,190 alleles · ultra-rare
exomes 78/1,453,882 · genomes 8/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0506% | 1,977 |
| European (non-Finnish) | 0.00628% | 15,912 |
| Admixed American | 0.00525% | 19,036 |
| South Asian | 0.00441% | 22,668 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,023 |
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.Gln450=
- Coding
- c.1350G>A
- MANE Select
- NM_006662
- dbSNP
- rs146916680
- Type
- single nucleotide variant
- Location
- chr16:30711602 (GRCh38)
- Gene constraint
- LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 450
- a UniProt-annotated variant site (in dehmba); the 'disordered' region
Similar variants
- SRCAP p.Gln450His Uncertain significance ★★ ⚠ same residue
- SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same condition
- SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same condition
- SRCAP p.Arg2444Ter Pathogenic ★★ same condition
- SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same condition
- SRCAP p.Arg2748Ter Pathogenic ★★ same condition
- SRCAP p.Gln2407Ter Pathogenic ★★ same condition
- SRCAP p.Gln2419Ter Pathogenic ★★ same condition
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-gln450 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown