Is CHAC2 p.Gly177Arg (c.529G>A) pathogenic?

CHAC2 p.Gly177Arg (c.529G>A) is classified Uncertain significance in CHAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: likely benign (0.0996); Rare (popmax 0.821%, afr).

How common is CHAC2 p.Gly177Arg (c.529G>A) in the general population?

CHAC2 p.Gly177Arg (c.529G>A) is rare (popmax 0.821%, afr) (gnomAD).

What do computational predictors say about CHAC2 p.Gly177Arg (c.529G>A)?

AlphaMissense predicts likely benign (score 0.0996) — an in-silico prediction, not a clinical call.

CHAC2 p.Gly177Arg

c.529G>A · VCV4227604

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0996 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.821%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0996	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -3.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.7	GERP 0.22, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 6,635 bp · p 0.0017 · regional, not allelic
Overall
CADD	14.9	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 0.821% African / African-American · 597/72,756 alleles

Filtering AF 0.766% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.744%

Overall 0.0415% 648/1,561,976 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.821%	122
Remaining individualsnot grpmax-eligible	0.0414%	2,414
Admixed American	0.0323%	3,094
Middle Eastern	0.0172%	5,800
European (non-Finnish)	0.000776%	128,790

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: CHAC2
Protein: p.Gly177Arg
Coding: c.529G>A
MANE Select: NM_016115 · reported on NM_001008708
Type: single nucleotide variant
Location: chr2:53774499 (GRCh38)

Full CHAC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/chac2-p-gly177arg (accessed [today's date]).

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