Is AUH p.Val158Asp (c.473T>A) pathogenic?

AUH p.Val158Asp (c.473T>A) is classified Uncertain significance in AUH (ClinVar, Single submitter, 1 submitter; last evaluated 2016-04-13). AlphaMissense: likely pathogenic (0.9962); Very rare (popmax 0.00133%, afr).

How common is AUH p.Val158Asp (c.473T>A) in the general population?

AUH p.Val158Asp (c.473T>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about AUH p.Val158Asp (c.473T>A)?

AlphaMissense predicts likely pathogenic (score 0.9962) — an in-silico prediction, not a clinical call.

AUH p.Val158Asp

c.473T>A · rs750201941 · VCV287535

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9962 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9962	likely pathogenic · top 3% in AUH
REVEL	0.61	indeterminate
SaProt	LLR -14.49	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 148 kb · p 0.51 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,922 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000744% 12/1,613,780 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,922
European (non-Finnish)	0.000932%	107,262

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: AUH
Protein: p.Val158Asp
Coding: c.473T>A
MANE Select: NM_001698
dbSNP: rs750201941
Type: single nucleotide variant
Location: chr9:91325350 (GRCh38)
Gene constraint: LOEUF 0.994 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.63 · 3 PDB
Residue 158: an α-helix

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

Similar variants

AUH p.Val158= Likely benign ★ same residue
AUH c.505+1G>C Pathogenic/Likely pathogenic ★★ same type
AUH p.Ala240Val Likely pathogenic ★★ same type
AUH p.Arg197Ter Pathogenic ★★ same type
AUH p.Arg241Ter Pathogenic/Likely pathogenic ★★ same type
AUH p.Trp50Ter Likely pathogenic ★★ same type
AUH c.655+3A>C Uncertain significance ★★ same type
AUH p.Ala117Val 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/auh-p-val158asp (accessed [today's date]).

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