Is CHAC2 p.Ala64Thr (c.190G>A) pathogenic?

CHAC2 p.Ala64Thr (c.190G>A) is classified Uncertain significance in CHAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-28). AlphaMissense: likely pathogenic (0.7288); Very rare (popmax 0.00168%, amr).

How common is CHAC2 p.Ala64Thr (c.190G>A) in the general population?

CHAC2 p.Ala64Thr (c.190G>A) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about CHAC2 p.Ala64Thr (c.190G>A)?

AlphaMissense predicts likely pathogenic (score 0.7288) — an in-silico prediction, not a clinical call.

CHAC2 p.Ala64Thr

c.190G>A · rs1674159114 · VCV2314202

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7288 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7288	likely pathogenic
REVEL	0.619	indeterminate
SaProt	LLR -11.19	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 6,635 bp · p 0.0017 · regional, not allelic
Overall
CADD	28.8	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 0.00168% Admixed American · 1/59,424 alleles

Overall 0.000124% 2/1,609,634 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00168%	59,424
European (non-Finnish)	8.49e-05%	1,178,098

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.Ala64Thr
Coding: c.190G>A
MANE Select: NM_016115 · reported on NM_001008708
dbSNP: rs1674159114
Type: single nucleotide variant
Location: chr2:53774160 (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-ala64thr (accessed [today's date]).

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