Is ARRDC2 p.Ala232Val (c.695C>T) pathogenic?

ARRDC2 p.Ala232Val (c.695C>T) is classified Uncertain significance in ARRDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.1173); Very rare (popmax 0.00144%, nfe).

How common is ARRDC2 p.Ala232Val (c.695C>T) in the general population?

ARRDC2 p.Ala232Val (c.695C>T) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about ARRDC2 p.Ala232Val (c.695C>T)?

AlphaMissense predicts likely benign (score 0.1173) — an in-silico prediction, not a clinical call.

ARRDC2 p.Ala232Val

c.695C>T · rs774002258 · VCV2471369

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1173 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1173	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.76	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,974 bp · p 0.65 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00144% European (non-Finnish) · 17/1,179,726 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00106% 17/1,610,720 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: ARRDC2
Protein: p.Ala232Val
Coding: c.695C>T
MANE Select: NM_015683
dbSNP: rs774002258
Type: single nucleotide variant
Location: chr19:18009885 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.70

Full ARRDC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARRDC2 p.Ala232Thr Uncertain significance ★ ⚠ same residue
ARRDC2 p.Ala10Pro Uncertain significance ★ same type
ARRDC2 p.Ala145Ser Uncertain significance ★ ⚠ same type
ARRDC2 p.Ala260Thr Uncertain significance ★ ⚠ same type
ARRDC2 p.Ala347Val Uncertain significance ★ ⚠ same type
ARRDC2 p.Ala353Thr Uncertain significance ★ ⚠ same type
ARRDC2 p.Ala375Ser Uncertain significance ★ ⚠ same type
ARRDC2 p.Ala375Thr 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/arrdc2-p-ala232val (accessed [today's date]).

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