Is ARPC1B p.Ala309= (c.927G>A) pathogenic?

ARPC1B p.Ala309= (c.927G>A) is classified Likely benign in ARPC1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). Very rare (popmax 0.00595%, sas).

How common is ARPC1B p.Ala309= (c.927G>A) in the general population?

ARPC1B p.Ala309= (c.927G>A) is very rare (popmax 0.00595%, sas) (gnomAD).

ARPC1B p.Ala309=

c.927G>A · VCV4771782

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00595%, sas)

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 -3.2	GERP -3.4
Overall
CADD	5.657	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00595% South Asian · 5/84,086 alleles

Filtering AF 0.00234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00146%

Overall 0.000358% 5/1,397,832 alleles · very rare

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.Ala309=
Coding: c.927G>A
MANE Select: NM_005720
Type: single nucleotide variant
Location: chr7:99392814 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 4 PDB

Full ARPC1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARPC1B p.Ala309Val 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-ala309 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown