ARPC1B p.Leu366=
c.1096T>C · rs759024145 · VCV1611989
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00949%, nfe)
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 0.023 | GERP -0.6, phastCons 0.9 |
| Overall | ||
| CADD | 6.833 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00949%
European (non-Finnish) · 112/1,180,008 alleles
Filtering AF
0.00804%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00752%
Overall
0.00725%
117/1,613,960 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00949% | 10,536 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| African / African-American | 0.00267% | 37,459 |
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.Leu366=
- Coding
- c.1096T>C
- MANE Select
- NM_005720
- dbSNP
- rs759024145
- Type
- single nucleotide variant
- Location
- chr7:99394466 (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-leu366 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown