Is ARPC1B p.Val208Phe (c.622G>T) pathogenic?

ARPC1B p.Val208Phe (c.622G>T) is classified Pathogenic in ARPC1B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-08-03). AlphaMissense: likely pathogenic (0.837); Absent from gnomAD v4.1; Associated with platelet abnormalities with eosinophilia and immune-mediated inflammatory disease.

How common is ARPC1B p.Val208Phe (c.622G>T) in the general population?

ARPC1B p.Val208Phe (c.622G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARPC1B p.Val208Phe (c.622G>T)?

AlphaMissense predicts likely pathogenic (score 0.837) — an in-silico prediction, not a clinical call.

ARPC1B p.Val208Phe

Q: What condition is associated with ARPC1B p.Val208Phe (c.622G>T)?

ARPC1B p.Val208Phe (c.622G>T) is associated with platelet abnormalities with eosinophilia and immune-mediated inflammatory disease (ClinVar).

c.622G>T · rs371760619 · VCV974768

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.837 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

platelet abnormalities with eosinophilia and immune-mediated inflammatory disease

Computational evidence

Protein change
AlphaMissense	0.837	likely pathogenic ✓ concordant with ClinVar
REVEL	0.741	pathogenic-leaning
SaProt	LLR -14.29	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.9	GERP 0.81, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 8,771 bp · p 0.0087 · regional, not allelic
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARPC1B
Protein: p.Val208Phe
Coding: c.622G>T
MANE Select: NM_005720
dbSNP: rs371760619
Type: single nucleotide variant
Location: chr7:99391014 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 4 PDB
Residue 208: 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.Val208Ile Uncertain significance ★★ ⚠ same residue
ARPC1B c.64+2T>A Pathogenic ★★ same condition
ARPC1B p.Ala261= Pathogenic ★★ same condition
ARPC1B p.Ala238Val Uncertain significance ★★ ⚠ 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-val208phe (accessed [today's date]).

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