ARPC1B p.Ala249=
c.747G>A · rs757633382 · VCV1908063
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 -3.1 | GERP -3.2 |
| Overall | ||
| CADD | 9.733 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/59,982 alleles
Filtering AF
0.00138%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00116%
Overall
0.00204%
33/1,613,946 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 19,994 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| South Asian | 0.0022% | 45,530 |
| European (non-Finnish) | 0.00203% | 49,167 |
| African / African-American | 0.00134% | 74,894 |
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.Ala249=
- Coding
- c.747G>A
- MANE Select
- NM_005720
- dbSNP
- rs757633382
- Type
- single nucleotide variant
- Location
- chr7:99391217 (GRCh38)
- Gene constraint
- LOEUF 0.876 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.81 · 4 PDB
- Residue 249
- a β-strand
Similar variants
- ARPC1B p.Ala249Val 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-ala249 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown