Is ARG2 p.Pro176= (c.528A>G) pathogenic?

ARG2 p.Pro176= (c.528A>G) is classified Likely benign in ARG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-09). Very rare (popmax 0.00221%, nfe).

How common is ARG2 p.Pro176= (c.528A>G) in the general population?

ARG2 p.Pro176= (c.528A>G) is very rare (popmax 0.00221%, nfe) (gnomAD).

ARG2 p.Pro176=

c.528A>G · rs376978713 · VCV757604

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00221%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.054, phastCons 1
Overall
CADD	8.986	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% European (non-Finnish) · 26/1,175,932 alleles

Filtering AF 0.00154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00131%

Overall 0.00162% 26/1,609,300 alleles · very rare exomes 22/1,457,080 · genomes 4/152,220 · 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: ARG2
Protein: p.Pro176=
Coding: c.528A>G
MANE Select: NM_001172
dbSNP: rs376978713
Type: single nucleotide variant
Location: chr14:67646649 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.55 · 18 PDB
Residue 176: an α-helix

Full ARG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARG2 p.Ala308= Benign/Likely benign ★★ same type
ARG2 p.Arg4Trp Likely benign ★★ same type
ARG2 p.Gly36= Benign ★★ same type
ARG2 p.Ala106Pro Uncertain significance ★ ⚠ same type
ARG2 p.Ala123Thr Uncertain significance ★ ⚠ same type
ARG2 p.Ala191Ser Uncertain significance ★ ⚠ same type
ARG2 p.Ala31Asp Uncertain significance ★ ⚠ same type
ARG2 p.Arg105Ser 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/arg2-p-pro176 (accessed [today's date]).

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