Is ARRDC2 p.Val266Met (c.796G>A) pathogenic?

ARRDC2 p.Val266Met (c.796G>A) is classified Uncertain significance in ARRDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.2482); Very rare (popmax 0.00267%, afr).

How common is ARRDC2 p.Val266Met (c.796G>A) in the general population?

ARRDC2 p.Val266Met (c.796G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ARRDC2 p.Val266Met (c.796G>A)?

AlphaMissense predicts likely benign (score 0.2482) — an in-silico prediction, not a clinical call.

ARRDC2 p.Val266Met

c.796G>A · rs752261569 · VCV2533139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2482 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2482	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -10.85	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,974 bp · p 0.65 · regional, not allelic
Overall
CADD	26.7	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

Grpmax group 0.00267% African / African-American · 2/74,894 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00025% 4/1,602,530 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,447
Remaining individualsnot grpmax-eligible	0.0016%	62,378
European (non-Finnish)	8.48e-05%	1,179,786

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.Val266Met
Coding: c.796G>A
MANE Select: NM_015683
dbSNP: rs752261569
Type: single nucleotide variant
Location: chr19:18009986 (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.Ala10Pro Uncertain significance ★ same type
ARRDC2 p.Ala145Ser Uncertain significance ★ ⚠ same type
ARRDC2 p.Ala232Thr Uncertain significance ★ ⚠ same type
ARRDC2 p.Ala232Val 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

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-val266met (accessed [today's date]).

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