Is ARRDC2 p.Arg2His (c.5G>A) pathogenic?

ARRDC2 p.Arg2His (c.5G>A) is classified Uncertain significance in ARRDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). Ultra-rare (popmax 0.0486%, sas).

How common is ARRDC2 p.Arg2His (c.5G>A) in the general population?

ARRDC2 p.Arg2His (c.5G>A) is ultra-rare (popmax 0.0486%, sas) (gnomAD).

ARRDC2 p.Arg2His

c.5G>A · rs530160304 · VCV2254127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0486%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.015	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.94
Overall
CADD	4.578	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0486% South Asian · 12/24,668 alleles

Filtering AF 0.028% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.00117% 14/1,198,132 alleles · ultra-rare exomes 12/1,046,376 · genomes 2/151,756 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0486%	2,056
Remaining individualsnot grpmax-eligible	0.00233%	42,880
African / African-American	0.00159%	62,912

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.Arg2His
Coding: c.5G>A
MANE Select: NM_015683 · reported on NM_001025604
dbSNP: rs530160304
Type: single nucleotide variant
Location: chr19:18001319 (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-arg2his (accessed [today's date]).

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