Is ADH1B p.Ser178= (c.534G>A) pathogenic?

ADH1B p.Ser178= (c.534G>A) is classified Likely benign in ADH1B (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-25). Ultra-rare (popmax 0.0204%, nfe).

How common is ADH1B p.Ser178= (c.534G>A) in the general population?

ADH1B p.Ser178= (c.534G>A) is ultra-rare (popmax 0.0204%, nfe) (gnomAD).

ADH1B p.Ser178=

c.534G>A · rs142861273 · VCV733848

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0204%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9	GERP -3.7
Overall
CADD	0.444	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0204% European (non-Finnish) · 241/1,180,036 alleles

Filtering AF 0.0182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0174%

Overall 0.0172% 277/1,614,064 alleles · ultra-rare exomes 250/1,461,878 · genomes 27/152,186 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0359%	2,785
European (non-Finnish)grpmax	0.0204%	4,896
Remaining individualsnot grpmax-eligible	0.0096%	10,414
Admixed American	0.00333%	29,995
African / African-American	0.00267%	37,464
East Asian	0.00223%	44,902
South Asian	0.0022%	45,540

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser178=
Coding: c.534G>A
MANE Select: NM_000668
dbSNP: rs142861273
Type: single nucleotide variant
Location: chr4:99315931 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.86 · 9 PDB
Residue 178: an α-helix

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.Val204= 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

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-ser178 (accessed [today's date]).

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