Is ARPC1B p.Ala261Val (c.782C>T) pathogenic?

ARPC1B p.Ala261Val (c.782C>T) is classified Uncertain significance in ARPC1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-20). AlphaMissense: ambiguous (0.5482); Very rare (popmax 0.00167%, amr); Associated with platelet abnormalities with eosinophilia and immune-mediated inflammatory disease.

How common is ARPC1B p.Ala261Val (c.782C>T) in the general population?

ARPC1B p.Ala261Val (c.782C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ARPC1B p.Ala261Val (c.782C>T)?

AlphaMissense predicts ambiguous (score 0.5482) — an in-silico prediction, not a clinical call.

ARPC1B p.Ala261Val

Q: What condition is associated with ARPC1B p.Ala261Val (c.782C>T)?

ARPC1B p.Ala261Val (c.782C>T) is associated with platelet abnormalities with eosinophilia and immune-mediated inflammatory disease (ClinVar).

c.782C>T · rs1405172360 · VCV1942141

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5482 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

platelet abnormalities with eosinophilia and immune-mediated inflammatory disease

Computational evidence

Protein change
AlphaMissense	0.5482	ambiguous
REVEL	0.346	indeterminate
SaProt	LLR -9.50	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 8,771 bp · p 0.0087 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,934 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000496% 8/1,612,930 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,934
South Asian	0.0011%	90,992
European (non-Finnish)	0.000509%	196,569

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.Ala261Val
Coding: c.782C>T
MANE Select: NM_005720
dbSNP: rs1405172360
Type: single nucleotide variant
Location: chr7:99391252 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 4 PDB
Residue 261: a β-strand

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

Disease context

platelet abnormalities with eosinophilia and immune-mediated inflammatory disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARPC1B p.Ala261= Pathogenic ★★ same residue
ARPC1B p.Ala261Ser Uncertain significance ★ ⚠ same residue
ARPC1B c.64+2T>A Pathogenic ★★ same condition
ARPC1B p.Ala238Val Uncertain significance ★★ ⚠ same condition
ARPC1B p.Arg103His Uncertain significance ★★ ⚠ same condition
ARPC1B p.Cys162Gly Uncertain significance ★★ ⚠ same condition
ARPC1B p.Gly39Ser Uncertain significance ★★ ⚠ same condition
ARPC1B p.Met350Arg Uncertain significance ★★ ⚠ same condition

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-ala261val (accessed [today's date]).

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