ARPC1B p.Ala274=
c.822C>T · rs1406511975 · VCV1965576
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00137%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.3 | GERP -3.1 |
| Overall | ||
| CADD | 0.592 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00137%
African / African-American · 1/72,950 alleles
Filtering AF
8.2e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.5e-05%
Overall
0.000323%
5/1,546,364 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00137% | 72,950 |
| European (non-Finnish) | 0.00035% | 286,100 |
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
- ARPC1B
- Protein
- p.Ala274=
- Coding
- c.822C>T
- MANE Select
- NM_005720
- dbSNP
- rs1406511975
- Type
- single nucleotide variant
- Location
- chr7:99392709 (GRCh38)
- Gene constraint
- LOEUF 0.876 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.81 · 4 PDB
- Residue 274
- a turn
Similar variants
- ARPC1B p.Ala274Thr Uncertain significance ★ ⚠ same residue
- ARPC1B c.392+2T>C Pathogenic ★★ same type
- ARPC1B c.64+2T>A Pathogenic ★★ same type
- ARPC1B p.Ala261= Pathogenic ★★ same type
- ARPC1B c.1080+4A>C Uncertain significance ★★ same type
- ARPC1B c.170-3C>T Uncertain significance ★★ same type
- ARPC1B c.501-5G>A Uncertain significance ★★ same type
- ARPC1B p.Ala238Val Uncertain significance ★★ ⚠ 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/arpc1b-p-ala274 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown