Is ADH6 p.Ile161Thr (c.482T>C) pathogenic?

ADH6 p.Ile161Thr (c.482T>C) is classified Uncertain significance in ADH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-19). AlphaMissense: ambiguous (0.3413); Very rare (popmax 0.000424%, nfe).

How common is ADH6 p.Ile161Thr (c.482T>C) in the general population?

ADH6 p.Ile161Thr (c.482T>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about ADH6 p.Ile161Thr (c.482T>C)?

AlphaMissense predicts ambiguous (score 0.3413) — an in-silico prediction, not a clinical call.

ADH6 p.Ile161Thr

c.482T>C · VCV4018695

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3413 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3413	ambiguous
REVEL	0.137	moderately benign-leaning
SaProt	LLR -13.30	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP -1.9
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.74 · regional, not allelic
Overall
CADD	22.0	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

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,846 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,726 alleles · very rare

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: ADH6
Protein: p.Ile161Thr
Coding: c.482T>C
MANE Select: NM_001102470
Type: single nucleotide variant
Location: chr4:99210167 (GRCh38)
Gene constraint: LOEUF 1.263 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.87

Full ADH6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADH6 p.Ala159Val Uncertain significance ★ ⚠ same type
ADH6 p.Ala20Thr Uncertain significance ★ ⚠ same type
ADH6 p.Ala217Thr Uncertain significance ★ ⚠ same type
ADH6 p.Ala278Thr Uncertain significance ★ ⚠ same type
ADH6 p.Ala281Thr Uncertain significance ★ ⚠ same type
ADH6 p.Ala359Gly Uncertain significance ★ ⚠ same type
ADH6 p.Arg130Ser Uncertain significance ★ ⚠ same type
ADH6 p.Arg313Cys 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/adh6-p-ile161thr (accessed [today's date]).

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