ARPC1B p.His222=
c.666C>T · rs751741478 · VCV1581045
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0183%, 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 -16 | GERP -3.7 |
| Overall | ||
| CADD | 1.061 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0183%
Admixed American · 11/59,966 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00786%
Overall
0.00397%
64/1,613,764 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0183% | 5,451 |
| African / African-American | 0.00801% | 12,489 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,825 |
| European (non-Finnish) | 0.00347% | 28,779 |
| East Asian | 0.00223% | 44,886 |
| South Asian | 0.0022% | 45,538 |
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.His222=
- Coding
- c.666C>T
- MANE Select
- NM_005720
- dbSNP
- rs751741478
- Type
- single nucleotide variant
- Location
- chr7:99391058 (GRCh38)
- Gene constraint
- LOEUF 0.876 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.81 · 4 PDB
Similar variants
- 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
- ARPC1B p.Ala249Val 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-his222 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown