Is ADH7 p.His271Arg (c.812A>G) pathogenic?

ADH7 p.His271Arg (c.812A>G) is classified Likely benign in ADH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). AlphaMissense: likely benign (0.0897); Ultra-rare (popmax 0.0165%, mid).

How common is ADH7 p.His271Arg (c.812A>G) in the general population?

ADH7 p.His271Arg (c.812A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ADH7 p.His271Arg (c.812A>G)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

ADH7 p.His271Arg

c.812A>G · rs764699940 · VCV3089266

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -2.20	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 -8.3	GERP -3.8
Regional constraint	o/e 1.17	unconstrained · MANE · 22 kb · p 0.00024 · regional, not allelic
Overall
CADD	0.052	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 H283R vs ClinVar H271R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,054 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000342% 5/1,460,788 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,054
East Asian	0.00223%	44,852
European (non-Finnish)	0.000254%	393,102

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.His271Arg
Coding: c.812A>G
MANE Select: NM_000673
dbSNP: rs764699940
Type: single nucleotide variant
Location: chr4:99420546 (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-his271arg (accessed [today's date]).

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