Is ARPC1B p.Ala238Val (c.713C>T) pathogenic?

ARPC1B p.Ala238Val (c.713C>T) is classified Uncertain significance in ARPC1B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-01-29). AlphaMissense: likely benign (0.1049); Ultra-rare (popmax 0.066%, mid); Associated with platelet abnormalities with eosinophilia and immune-mediated inflammatory disease.

How common is ARPC1B p.Ala238Val (c.713C>T) in the general population?

ARPC1B p.Ala238Val (c.713C>T) is ultra-rare (popmax 0.066%, mid) (gnomAD).

What do computational predictors say about ARPC1B p.Ala238Val (c.713C>T)?

AlphaMissense predicts likely benign (score 0.1049) — an in-silico prediction, not a clinical call.

ARPC1B p.Ala238Val

Q: What condition is associated with ARPC1B p.Ala238Val (c.713C>T)?

ARPC1B p.Ala238Val (c.713C>T) is associated with platelet abnormalities with eosinophilia and immune-mediated inflammatory disease (ClinVar).

c.713C>T · rs369966813 · VCV1301680

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1049 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

platelet abnormalities with eosinophilia and immune-mediated inflammatory disease

Computational evidence

Protein change
AlphaMissense	0.1049	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -5.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.7, phastCons 0.99
Regional constraint	o/e 0.89	unconstrained · MANE · 8,771 bp · p 0.0087 · regional, not allelic
Overall
CADD	17.65	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00434% 70/1,614,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0128%	7,814
South Asian	0.011%	9,106
European (non-Finnish)	0.00381%	26,222
Admixed American	0.00333%	29,997
African / African-American	0.00133%	75,026

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.Ala238Val
Coding: c.713C>T
MANE Select: NM_005720
dbSNP: rs369966813
Type: single nucleotide variant
Location: chr7:99391183 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 4 PDB
Residue 238: a UniProt-annotated variant site (in imd71; uncertain significance); 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.Ala238Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
ARPC1B p.Ala238= Likely benign ★ same residue
ARPC1B c.64+2T>A Pathogenic ★★ same condition
ARPC1B p.Ala261= Pathogenic ★★ same condition
ARPC1B p.Ala261Val 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

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-ala238val (accessed [today's date]).

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