Is ARRDC2 p.Ala10Pro (c.28G>C) pathogenic?

ARRDC2 p.Ala10Pro (c.28G>C) is classified Uncertain significance in ARRDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). Very rare (popmax 0.00319%, afr).

How common is ARRDC2 p.Ala10Pro (c.28G>C) in the general population?

ARRDC2 p.Ala10Pro (c.28G>C) is very rare (popmax 0.00319%, afr) (gnomAD).

ARRDC2 p.Ala10Pro

c.28G>C · rs1045114947 · VCV2206101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00319%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.03	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.61
Overall
CADD	19.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00319% African / African-American · 2/62,730 alleles

Filtering AF 0.000529% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000198%

Overall 0.000167% 2/1,194,792 alleles · very rare exomes 0/1,043,352 · genomes 2/151,440 · joint denominator

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.Ala10Pro
Coding: c.28G>C
MANE Select: NM_015683 · reported on NM_001025604
dbSNP: rs1045114947
Type: single nucleotide variant
Location: chr19:18001342 (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.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
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-ala10pro (accessed [today's date]).

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