Is ADH1B p.Val204= (c.612C>T) pathogenic?

ADH1B p.Val204= (c.612C>T) is classified Benign in ADH1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 7.29%, afr) — too common for a highly-penetrant pathogenic allele.

ADH1B p.Val204=

Q: How common is ADH1B p.Val204= (c.612C>T) in the general population?

ADH1B p.Val204= (c.612C>T) is common (popmax 7.29%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.612C>T · rs28626993 · VCV772869

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.29%, afr) — too common for a highly-penetrant pathogenic allele

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 -10	GERP -3.7
Overall
CADD	0.587	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.29% African / African-American · 5,468/75,004 alleles

Filtering AF 7.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.06%

Overall 0.371% 5,993/1,614,150 alleles · common exomes 2,926/1,461,890 · genomes 3,067/152,260 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.29%	14
Remaining individualsnot grpmax-eligible	0.422%	237
Admixed American	0.265%	377
Middle Eastern	0.148%	674
South Asian	0.00878%	11,386
European (non-Finnish)	0.0072%	13,883

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: ADH1B
Protein: p.Val204=
Coding: c.612C>T
MANE Select: NM_000668
dbSNP: rs28626993
Type: single nucleotide variant
Location: chr4:99314037 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.86 · 9 PDB
Residue 204: an α-helix; a binding site

Full ADH1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADH1B p.Ala222= Benign ★★ same type
ADH1B p.Ser165= Benign ★★ same type
ADH1B p.Trp16Arg Benign ★★ same type
ADH1B p.Ala164Ser Uncertain significance ★ ⚠ same type
ADH1B p.Ala222Val Uncertain significance ★ ⚠ same type
ADH1B p.Ala238Val Uncertain significance ★ ⚠ same type
ADH1B p.Ala345Val Uncertain significance ★ ⚠ same type
ADH1B p.Arg134Ser 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/adh1b-p-val204 (accessed [today's date]).

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