Is ADH7 p.Arg38His (c.113G>A) pathogenic?

ADH7 p.Arg38His (c.113G>A) is classified Likely benign in ADH7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-31). AlphaMissense: likely pathogenic (0.7955); Rare (popmax 0.416%, afr); Associated with ADH7-related disorder.

What condition is associated with ADH7 p.Arg38His (c.113G>A)?

ADH7 p.Arg38His (c.113G>A) is associated with ADH7-related disorder (ClinVar).

How common is ADH7 p.Arg38His (c.113G>A) in the general population?

ADH7 p.Arg38His (c.113G>A) is rare (popmax 0.416%, afr) (gnomAD).

What do computational predictors say about ADH7 p.Arg38His (c.113G>A)?

AlphaMissense predicts likely pathogenic (score 0.7955) — an in-silico prediction, not a clinical call.

ADH7 p.Arg38His

c.113G>A · rs148026590 · VCV3044463

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7955 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.416%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ADH7-related disorder

Computational evidence

Protein change
AlphaMissense	0.7955	likely pathogenic
REVEL	0.195	benign-leaning
SaProt	LLR -14.96	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -1.1
Regional constraint	o/e 1.17	unconstrained · MANE · 22 kb · p 0.00024 · regional, not allelic
Overall
CADD	21.1	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 R50H vs ClinVar R38H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.416% African / African-American · 312/74,986 alleles

Filtering AF 0.378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.363%

Overall 0.0225% 363/1,610,322 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.416%	240
Remaining individualsnot grpmax-eligible	0.0241%	4,157
Admixed American	0.0117%	8,531
East Asian	0.00446%	22,418
South Asian	0.00443%	22,595
European (non-Finnish)	0.00195%	51,211

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.Arg38His
Coding: c.113G>A
MANE Select: NM_000673
dbSNP: rs148026590
Type: single nucleotide variant
Location: chr4:99429539 (GRCh38)
Gene constraint: LOEUF 1.429 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.13 · 3 PDB
Residue 38: 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.Ala158= 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-arg38his (accessed [today's date]).

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