Is ADH7 p.Ala158= (c.474T>C) pathogenic?

ADH7 p.Ala158= (c.474T>C) is classified Likely benign in ADH7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-06-27). Ultra-rare (popmax 0.0165%, mid); Associated with ADH7-related disorder.

What condition is associated with ADH7 p.Ala158= (c.474T>C)?

ADH7 p.Ala158= (c.474T>C) is associated with ADH7-related disorder (ClinVar).

How common is ADH7 p.Ala158= (c.474T>C) in the general population?

ADH7 p.Ala158= (c.474T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

ADH7 p.Ala158=

c.474T>C · rs750979953 · VCV3046065

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

ADH7-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -3.8
Overall
CADD	0.125	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00995%

Overall 0.00961% 155/1,613,462 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
European (non-Finnish)	0.0122%	8,193
Remaining individualsnot grpmax-eligible	0.0096%	10,412
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,791
Admixed American	0.00334%	29,951

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.Ala158=
Coding: c.474T>C
MANE Select: NM_000673
dbSNP: rs750979953
Type: single nucleotide variant
Location: chr4:99427863 (GRCh38)
Gene constraint: LOEUF 1.429 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.13 · 3 PDB
Residue 158: a β-strand

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

Disease context

ADH7-related disorder

Similar variants

ADH7 p.Lys40Thr Uncertain significance ★ ⚠ same condition
ADH7 p.Arg120Cys Uncertain significance ⚠ same condition
ADH7 p.Thr186= Uncertain significance same condition
ADH7 c.120+7G>A Likely benign same condition
ADH7 c.121-6A>G Benign same condition
ADH7 c.-35T>C Likely benign same condition
ADH7 c.-4C>T Likely benign same condition
ADH7 p.Arg120His Likely benign same condition

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-ala158 (accessed [today's date]).

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