Is ADH6 p.Glu339Asp (c.1017G>T) pathogenic?

ADH6 p.Glu339Asp (c.1017G>T) is classified Uncertain significance in ADH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: likely benign (0.1295); Very rare (popmax 0.00111%, sas).

How common is ADH6 p.Glu339Asp (c.1017G>T) in the general population?

ADH6 p.Glu339Asp (c.1017G>T) is very rare (popmax 0.00111%, sas) (gnomAD).

What do computational predictors say about ADH6 p.Glu339Asp (c.1017G>T)?

AlphaMissense predicts likely benign (score 0.1295) — an in-silico prediction, not a clinical call.

ADH6 p.Glu339Asp

c.1017G>T · VCV3501128

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1295 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1295	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -0.97
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.74 · regional, not allelic
Overall
CADD	13.54	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 0.00111% South Asian · 1/90,248 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000412% 6/1,456,366 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	90,248
European (non-Finnish)	0.000425%	235,486

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: ADH6
Protein: p.Glu339Asp
Coding: c.1017G>T
MANE Select: NM_001102470
Type: single nucleotide variant
Location: chr4:99205011 (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-glu339asp (accessed [today's date]).

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