Is ARPC1B p.Met350Arg (c.1049T>G) pathogenic?

ARPC1B p.Met350Arg (c.1049T>G) is classified Uncertain significance in ARPC1B (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-10-27). AlphaMissense: likely pathogenic (0.7868); Rare (popmax 0.177%, nfe); Associated with platelet abnormalities with eosinophilia and immune-mediated inflammatory disease.

How common is ARPC1B p.Met350Arg (c.1049T>G) in the general population?

ARPC1B p.Met350Arg (c.1049T>G) is rare (popmax 0.177%, nfe) (gnomAD).

What do computational predictors say about ARPC1B p.Met350Arg (c.1049T>G)?

AlphaMissense predicts likely pathogenic (score 0.7868) — an in-silico prediction, not a clinical call.

ARPC1B p.Met350Arg

Q: What condition is associated with ARPC1B p.Met350Arg (c.1049T>G)?

ARPC1B p.Met350Arg (c.1049T>G) is associated with platelet abnormalities with eosinophilia and immune-mediated inflammatory disease (ClinVar).

c.1049T>G · rs151225927 · VCV1053497

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.7868 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.177%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

platelet abnormalities with eosinophilia and immune-mediated inflammatory disease

Computational evidence

Protein change
AlphaMissense	0.7868	likely pathogenic
REVEL	0.444	indeterminate
SaProt	LLR -12.10	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.66, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 8,771 bp · p 0.0087 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.177% European (non-Finnish) · 2,086/1,180,028 alleles

Filtering AF 0.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.168%

Overall 0.14% 2,259/1,613,728 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.177%	566
Remaining individualsnot grpmax-eligible	0.133%	753
Admixed American	0.0899%	1,112
African / African-American	0.0386%	2,589
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
Finnishnot grpmax-eligible	0.0063%	15,884

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.Met350Arg
Coding: c.1049T>G
MANE Select: NM_005720
dbSNP: rs151225927
Type: single nucleotide variant
Location: chr7:99394088 (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

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 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
ARPC1B p.Ser311Cys 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-met350arg (accessed [today's date]).

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