Is ADH7 p.Glu239Val (c.716A>T) pathogenic?

ADH7 p.Glu239Val (c.716A>T) is classified Uncertain significance in ADH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: ambiguous (0.4335); Very rare (popmax 0.005%, amr).

How common is ADH7 p.Glu239Val (c.716A>T) in the general population?

ADH7 p.Glu239Val (c.716A>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ADH7 p.Glu239Val (c.716A>T)?

AlphaMissense predicts ambiguous (score 0.4335) — an in-silico prediction, not a clinical call.

ADH7 p.Glu239Val

c.716A>T · VCV3838276

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4335 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
AlphaMissense	0.4335	ambiguous
REVEL	0.294	indeterminate
SaProt	LLR -10.79	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.9, phastCons 0.99
Regional constraint	o/e 1.17	unconstrained · MANE · 22 kb · p 0.00024 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E251V vs ClinVar E239V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,954 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00198% 29/1,461,728 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,985
European (non-Finnish)	0.00212%	47,197
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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: ADH7
Protein: p.Glu239Val
Coding: c.716A>T
MANE Select: NM_000673
Type: single nucleotide variant
Location: chr4:99420642 (GRCh38)
Gene constraint: LOEUF 1.429 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.13 · 3 PDB
Residue 239: an α-helix

Full ADH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADH7 p.Lys226Glu Benign ★★ ⚠ same type
ADH7 c.-18A>T Uncertain significance ★ ⚠ same type
ADH7 c.-4C>G Uncertain significance ★ ⚠ same type
ADH7 p.Ala13Ser Uncertain significance ★ same type
ADH7 p.Ala278Ser Uncertain significance ★ ⚠ same type
ADH7 p.Ala278Thr Uncertain significance ★ same type
ADH7 p.Ala298Val Uncertain significance ★ ⚠ same type
ADH7 p.Arg105Cys 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/adh7-p-glu239val (accessed [today's date]).

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