Is ARPC4 p.Ile114Val (c.340A>G) pathogenic?

ARPC4 p.Ile114Val (c.340A>G) is classified Uncertain significance in ARPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.2358); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ARPC4 p.Ile114Val (c.340A>G)?

ARPC4 p.Ile114Val (c.340A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ARPC4 p.Ile114Val (c.340A>G) in the general population?

ARPC4 p.Ile114Val (c.340A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARPC4 p.Ile114Val (c.340A>G)?

AlphaMissense predicts likely benign (score 0.2358) — an in-silico prediction, not a clinical call.

ARPC4 p.Ile114Val

c.340A>G · VCV3948581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2358 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2358	likely benign
REVEL	0.557	indeterminate
SaProt	LLR -10.31	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 13 kb · p 7.2e-15 · regional, not allelic
Overall
CADD	22.4	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.Ile114Val
Coding: c.340A>G
MANE Select: NM_005718
Type: single nucleotide variant
Location: chr3:9803852 (GRCh38)
Gene constraint: LOEUF 0.362 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.20 · 5 PDB
Residue 114: 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-ile114val (accessed [today's date]).

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