Is ADH6 p.Gly142Arg (c.424G>C) pathogenic?

ADH6 p.Gly142Arg (c.424G>C) is classified Uncertain significance in ADH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-06). AlphaMissense: likely pathogenic (0.5874); Absent from gnomAD v4.1.

How common is ADH6 p.Gly142Arg (c.424G>C) in the general population?

ADH6 p.Gly142Arg (c.424G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADH6 p.Gly142Arg (c.424G>C)?

AlphaMissense predicts likely pathogenic (score 0.5874) — an in-silico prediction, not a clinical call.

ADH6 p.Gly142Arg

c.424G>C · VCV4638486

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5874 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5874	likely pathogenic
REVEL	0.123	moderately benign-leaning
SaProt	LLR -4.48	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -3.7
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.74 · regional, not allelic
Overall
CADD	0.747	PHRED · no single calibrated threshold — expert panels disagree

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: ADH6
Protein: p.Gly142Arg
Coding: c.424G>C
MANE Select: NM_001102470
Type: single nucleotide variant
Location: chr4:99210225 (GRCh38)
Gene constraint: LOEUF 1.263 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.87

Full ADH6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADH6 p.Ala159Val Uncertain significance ★ ⚠ same type
ADH6 p.Ala20Thr Uncertain significance ★ ⚠ same type
ADH6 p.Ala217Thr Uncertain significance ★ ⚠ same type
ADH6 p.Ala278Thr Uncertain significance ★ ⚠ same type
ADH6 p.Ala281Thr Uncertain significance ★ ⚠ same type
ADH6 p.Ala359Gly Uncertain significance ★ ⚠ same type
ADH6 p.Arg130Ser Uncertain significance ★ ⚠ same type
ADH6 p.Arg313Cys 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/adh6-p-gly142arg (accessed [today's date]).

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