Is ADH1B p.Phe323Ser (c.968T>C) pathogenic?

ADH1B p.Phe323Ser (c.968T>C) is classified Uncertain significance in ADH1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: likely pathogenic (0.7815); Absent from gnomAD v4.1.

How common is ADH1B p.Phe323Ser (c.968T>C) in the general population?

ADH1B p.Phe323Ser (c.968T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADH1B p.Phe323Ser (c.968T>C)?

AlphaMissense predicts likely pathogenic (score 0.7815) — an in-silico prediction, not a clinical call.

ADH1B p.Phe323Ser

c.968T>C · VCV4018399

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7815 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7815	likely pathogenic
REVEL	0.071	moderately benign-leaning
SaProt	LLR -7.63	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -3.7
Regional constraint	o/e 0.86	unconstrained · MANE · 6,039 bp · p 0.076 · regional, not allelic
Overall
CADD	9.559	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADH1B
Protein: p.Phe323Ser
Coding: c.968T>C
MANE Select: NM_000668
Type: single nucleotide variant
Location: chr4:99310900 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.86 · 9 PDB

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-phe323ser (accessed [today's date]).

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