SNAPC4 p.Ala653=
c.1959G>A · VCV4821960
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0173%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6 | GERP -2.1 |
| Overall | ||
| CADD | 0.739 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0173%
Middle Eastern · 1/5,784 alleles
Filtering AF
0.00179%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00107%
Overall
0.00135%
21/1,551,962 alleles · ultra-rare
exomes 17/1,399,714 · genomes 4/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0173% | 5,784 |
| African / African-American | 0.00552% | 18,114 |
| South Asian | 0.00365% | 27,397 |
| Remaining individualsnot grpmax-eligible | 0.00336% | 29,786 |
| European (non-Finnish) | 0.000955% | 104,718 |
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
- SNAPC4
- Protein
- p.Ala653=
- Coding
- c.1959G>A
- MANE Select
- NM_003086
- Type
- single nucleotide variant
- Location
- chr9:136383210 (GRCh38)
- Gene constraint
- LOEUF 0.995 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 53.61 · 18 PDB
- Residue 653
- the 'disordered' region
Similar variants
- SNAPC4 p.Ala653Val Likely benign ★ same residue
- SNAPC4 p.Ala1193Gly Uncertain significance ★★ ⚠ same type
- SNAPC4 p.Ala437Thr Uncertain significance ★★ ⚠ same type
- SNAPC4 p.Arg640Lys Uncertain significance ★★ ⚠ same type
- SNAPC4 p.Asp436Asn Uncertain significance ★★ ⚠ same type
- SNAPC4 p.Glu546Asp Uncertain significance ★★ ⚠ same type
- SNAPC4 p.Leu831Phe Uncertain significance ★★ ⚠ same type
- SNAPC4 p.Gly525Ser Likely benign ★★ 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/snapc4-p-ala653 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown