Is ARPC4 p.Arg32Gln (c.95G>A) pathogenic?

ARPC4 p.Arg32Gln (c.95G>A) is classified Uncertain significance in ARPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-13). AlphaMissense: likely pathogenic (0.9826); Very rare (popmax 0.000508%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ARPC4 p.Arg32Gln (c.95G>A)?

ARPC4 p.Arg32Gln (c.95G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ARPC4 p.Arg32Gln (c.95G>A) in the general population?

ARPC4 p.Arg32Gln (c.95G>A) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about ARPC4 p.Arg32Gln (c.95G>A)?

AlphaMissense predicts likely pathogenic (score 0.9826) — an in-silico prediction, not a clinical call.

ARPC4 p.Arg32Gln

c.95G>A · VCV4148082

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9826 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9826	likely pathogenic
REVEL	0.405	indeterminate
SaProt	LLR -15.38	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 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 13 kb · p 7.2e-15 · regional, not allelic
Overall
CADD	33.0	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 0.000508% European (non-Finnish) · 6/1,180,022 alleles

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

Overall 0.00041% 6/1,461,818 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: ARPC4
Protein: p.Arg32Gln
Coding: c.95G>A
MANE Select: NM_005718
Type: single nucleotide variant
Location: chr3:9797750 (GRCh38)
Gene constraint: LOEUF 0.362 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.20 · 5 PDB
Residue 32: a β-strand

Full ARPC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARPC4 c.3+11C>G Uncertain significance ★ same condition
ARPC4 c.3+11C>T Uncertain significance ★ same condition
ARPC4 c.3+16C>T Uncertain significance ★ same condition
ARPC4 c.3+17C>A Uncertain significance ★ same condition
ARPC4 c.3+20G>A Uncertain significance ★ same condition
ARPC4 c.3+38G>A Uncertain significance ★ same condition
ARPC4 c.3+47C>T Uncertain significance ★ same condition
ARPC4 c.3+55T>G 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/arpc4-p-arg32gln (accessed [today's date]).

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