Is ALDH2 p.Arg342Pro (c.1025G>C) pathogenic?

ALDH2 p.Arg342Pro (c.1025G>C) is classified Uncertain significance in ALDH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). AlphaMissense: likely pathogenic (0.9852); Absent from gnomAD v4.1.

How common is ALDH2 p.Arg342Pro (c.1025G>C) in the general population?

ALDH2 p.Arg342Pro (c.1025G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALDH2 p.Arg342Pro (c.1025G>C)?

AlphaMissense predicts likely pathogenic (score 0.9852) — an in-silico prediction, not a clinical call.

ALDH2 p.Arg342Pro

c.1025G>C · rs775082307 · VCV2360699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9852 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9852	likely pathogenic · top 9% in ALDH2
REVEL	0.821	moderately pathogenic-leaning
SaProt	LLR -16.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 43 kb · p 1.7e-06 · regional, not allelic
Overall
CADD	29.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALDH2
Protein: p.Arg342Pro
Coding: c.1025G>C
MANE Select: NM_000690
dbSNP: rs775082307
Type: single nucleotide variant
Location: chr12:111792724 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.02 · 29 PDB
Residue 342: an α-helix

Full ALDH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALDH2 p.Ile41Val Likely benign ★★ same type
ALDH2 p.Pro92Thr Benign ★★ ⚠ same type
ALDH2 p.Thr244Met Likely benign ★★ ⚠ same type
ALDH2 p.Val304Met Benign ★★ same type
ALDH2 p.Arg114Gln Uncertain significance ★ ⚠ same type
ALDH2 p.Arg116Trp Uncertain significance ★ ⚠ same type
ALDH2 p.Arg268Cys Uncertain significance ★ ⚠ same type
ALDH2 p.Asn516His 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/aldh2-p-arg342pro (accessed [today's date]).

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