Is ADH6 p.Lys331Ile (c.992A>T) pathogenic?

ADH6 p.Lys331Ile (c.992A>T) is classified Uncertain significance in ADH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). AlphaMissense: likely benign (0.2457); Absent from gnomAD v4.1.

How common is ADH6 p.Lys331Ile (c.992A>T) in the general population?

ADH6 p.Lys331Ile (c.992A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADH6 p.Lys331Ile (c.992A>T)?

AlphaMissense predicts likely benign (score 0.2457) — an in-silico prediction, not a clinical call.

ADH6 p.Lys331Ile

c.992A>T · VCV4018705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2457 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2457	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -10.86	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -2.8
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.74 · regional, not allelic
Overall
CADD	16.59	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.Lys331Ile
Coding: c.992A>T
MANE Select: NM_001102470
Type: single nucleotide variant
Location: chr4:99205036 (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-lys331ile (accessed [today's date]).

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