Is ARRDC2 p.Arg262Gln (c.785G>A) pathogenic?

ARRDC2 p.Arg262Gln (c.785G>A) is classified Uncertain significance in ARRDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-21). AlphaMissense: likely benign (0.1055); Low-frequency (popmax 1.09%, afr).

How common is ARRDC2 p.Arg262Gln (c.785G>A) in the general population?

ARRDC2 p.Arg262Gln (c.785G>A) is low-frequency (popmax 1.09%, afr) (gnomAD).

What do computational predictors say about ARRDC2 p.Arg262Gln (c.785G>A)?

AlphaMissense predicts likely benign (score 0.1055) — an in-silico prediction, not a clinical call.

ARRDC2 p.Arg262Gln

c.785G>A · rs115826747 · VCV2920783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1055 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.09%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1055	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -8.49	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 0.66	phastCons 0.063
Regional constraint	o/e 0.98	unconstrained · MANE · 1,974 bp · p 0.65 · regional, not allelic
Overall
CADD	22.2	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 1.09% African / African-American · 815/75,024 alleles

Filtering AF 1.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 1%

Overall 0.0923% 1,480/1,603,204 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.09%	92
East Asian	0.684%	146
Middle Eastern	0.151%	663
Admixed American	0.122%	818
Remaining individualsnot grpmax-eligible	0.0962%	1,040
European (non-Finnish)	0.018%	5,565
South Asian	0.00439%	22,763

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.Arg262Gln
Coding: c.785G>A
MANE Select: NM_015683
dbSNP: rs115826747
Type: single nucleotide variant
Location: chr19:18009975 (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.Arg262Trp Uncertain significance ★ ⚠ same residue
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

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-arg262gln (accessed [today's date]).

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