Is ADH1A p.Ser266= (c.798A>G) pathogenic?

ADH1A p.Ser266= (c.798A>G) is classified Likely benign in ADH1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). Ultra-rare (popmax 0.0132%, sas).

How common is ADH1A p.Ser266= (c.798A>G) in the general population?

ADH1A p.Ser266= (c.798A>G) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

ADH1A p.Ser266=

c.798A>G · VCV3838050

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

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 -14	GERP -3.7
Overall
CADD	0.118	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% South Asian · 12/91,084 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00427% 69/1,614,070 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,590
East Asian	0.00446%	22,442
European (non-Finnish)	0.00432%	23,136
Admixed American	0.00333%	30,009
Remaining individualsnot grpmax-eligible	0.0016%	62,504
African / African-American	0.00133%	75,050

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: ADH1A
Protein: p.Ser266=
Coding: c.798A>G
MANE Select: NM_000667
Type: single nucleotide variant
Location: chr4:99282376 (GRCh38)
Gene constraint: LOEUF 1.104 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.97 · 2 PDB
Residue 266: a β-strand

Full ADH1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADH1A p.Ser266Thr Uncertain significance ★ ⚠ same residue
ADH1A p.Ala184Val Uncertain significance ★ ⚠ same type
ADH1A p.Ala222Val Uncertain significance ★ ⚠ same type
ADH1A p.Arg38His Uncertain significance ★ same type
ADH1A p.Asn156Ser Uncertain significance ★ ⚠ same type
ADH1A p.Asp298Gly Uncertain significance ★ ⚠ same type
ADH1A p.Asp50Glu Uncertain significance ★ ⚠ same type
ADH1A p.Cys101Phe 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/adh1a-p-ser266 (accessed [today's date]).

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