Is ARRDC2 p.Asp156Gly (c.467A>G) pathogenic?

ARRDC2 p.Asp156Gly (c.467A>G) is classified Uncertain significance in ARRDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-05). AlphaMissense: likely pathogenic (0.9233); Very rare (popmax 0.000424%, nfe).

How common is ARRDC2 p.Asp156Gly (c.467A>G) in the general population?

ARRDC2 p.Asp156Gly (c.467A>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about ARRDC2 p.Asp156Gly (c.467A>G)?

AlphaMissense predicts likely pathogenic (score 0.9233) — an in-silico prediction, not a clinical call.

ARRDC2 p.Asp156Gly

c.467A>G · VCV3948934

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9233 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9233	likely pathogenic · top 8% in ARRDC2
REVEL	0.705	pathogenic-leaning
SaProt	LLR -13.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,974 bp · p 0.65 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000424% European (non-Finnish) · 5/1,179,960 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,386 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.Asp156Gly
Coding: c.467A>G
MANE Select: NM_015683
Type: single nucleotide variant
Location: chr19:18009096 (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-asp156gly (accessed [today's date]).

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