Is ARPC4 p.Arg158= (c.474C>T) pathogenic?

ARPC4 p.Arg158= (c.474C>T) is classified Likely benign in ARPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-01). Rare (popmax 0.205%, afr).

How common is ARPC4 p.Arg158= (c.474C>T) in the general population?

ARPC4 p.Arg158= (c.474C>T) is rare (popmax 0.205%, afr) (gnomAD).

ARPC4 p.Arg158=

c.474C>T · VCV4821596

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.205%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.197	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.001	GERP -1.9, phastCons 0.8
Overall
CADD	10.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.205% African / African-American · 154/75,046 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.169%

Overall 0.0113% 183/1,614,198 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.205%	487
Admixed American	0.0233%	4,287
Remaining individualsnot grpmax-eligible	0.0192%	5,209
Middle Eastern	0.0165%	6,058
European (non-Finnish)	0.000169%	590,023

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.Arg158=
Coding: c.474C>T
MANE Select: NM_005718
Type: single nucleotide variant
Location: chr3:9803986 (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.Arg158His Pathogenic ★ same residue
ARPC4 p.Arg158Cys Conflicting classifications of pathogenicity ★ ⚠ 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-arg158 (accessed [today's date]).

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