Is ADH7 p.Cys317Trp (c.951T>G) pathogenic?

ADH7 p.Cys317Trp (c.951T>G) is classified Uncertain significance in ADH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely pathogenic (0.9644); Very rare (popmax 0.00167%, amr).

How common is ADH7 p.Cys317Trp (c.951T>G) in the general population?

ADH7 p.Cys317Trp (c.951T>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ADH7 p.Cys317Trp (c.951T>G)?

AlphaMissense predicts likely pathogenic (score 0.9644) — an in-silico prediction, not a clinical call.

ADH7 p.Cys317Trp

c.951T>G · VCV4244069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9644 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9644	likely pathogenic · top 7% in ADH7
REVEL	0.138	moderately benign-leaning
SaProt	LLR -13.60	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.33	donor loss, 10 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -1.3	GERP -3.5
Regional constraint	o/e 1.17	unconstrained · MANE · 22 kb · p 0.00024 · regional, not allelic
Overall
CADD	19.08	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 C329W vs ClinVar C317W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,962 alleles

Overall 6.84e-05% 1/1,461,432 alleles · very rare

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.Cys317Trp
Coding: c.951T>G
MANE Select: NM_000673
Type: single nucleotide variant
Location: chr4:99418996 (GRCh38)
Gene constraint: LOEUF 1.429 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.13 · 3 PDB

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-cys317trp (accessed [today's date]).

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