Is ARPC4 p.Arg158His (c.473G>A) pathogenic?

ARPC4 p.Arg158His (c.473G>A) is classified Pathogenic in ARPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-12). AlphaMissense: likely pathogenic (0.9984); Absent from gnomAD v4.1.

How common is ARPC4 p.Arg158His (c.473G>A) in the general population?

ARPC4 p.Arg158His (c.473G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARPC4 p.Arg158His (c.473G>A)?

AlphaMissense predicts likely pathogenic (score 0.9984) — an in-silico prediction, not a clinical call.

ARPC4 p.Arg158His

c.473G>A · VCV4891492

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9984 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9984	likely pathogenic ✓ concordant with ClinVar · top 9% in ARPC4
REVEL	0.596	indeterminate
SaProt	LLR -13.51	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 1.7, 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

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: ARPC4
Protein: p.Arg158His
Coding: c.473G>A
MANE Select: NM_005718
Type: single nucleotide variant
Location: chr3:9803985 (GRCh38)
Gene constraint: LOEUF 0.362 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.20 · 5 PDB
Residue 158: an α-helix; a UniProt-annotated variant site (in devlo)

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

Similar variants

ARPC4 p.Arg158Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
ARPC4 p.Arg158= Likely benign ★ same residue
ARPC4 c.3+11C>G Uncertain significance ★ same type
ARPC4 c.3+11C>T Uncertain significance ★ same type
ARPC4 c.3+14G>C Uncertain significance ★ same type
ARPC4 c.3+16C>T Uncertain significance ★ same type
ARPC4 c.3+17C>A Uncertain significance ★ same type
ARPC4 c.3+20G>A Uncertain significance ★ same type

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-arg158his (accessed [today's date]).

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