Is ASB9 p.Ala181Val (c.542C>T) pathogenic?

ASB9 p.Ala181Val (c.542C>T) is classified Uncertain significance in ASB9 (ClinVar, Single submitter, 3 submitters; last evaluated 2025-04-24). AlphaMissense: likely benign (0.1075); Ultra-rare (popmax 0.0355%, eas).

How common is ASB9 p.Ala181Val (c.542C>T) in the general population?

ASB9 p.Ala181Val (c.542C>T) is ultra-rare (popmax 0.0355%, eas) (gnomAD).

What do computational predictors say about ASB9 p.Ala181Val (c.542C>T)?

AlphaMissense predicts likely benign (score 0.1075) — an in-silico prediction, not a clinical call.

ASB9 p.Ala181Val

c.542C>T · rs779282972 · VCV1206096

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1075 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0355%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1075	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -8.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -2, phastCons 0.7
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.38 · regional, not allelic
Overall
CADD	10.76	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0355% East Asian · 12/33,844 alleles

Filtering AF 0.0204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00155% 17/1,097,066 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0355%	2,820
Remaining individualsnot grpmax-eligible	0.0105%	9,522

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: ASB9
Protein: p.Ala181Val
Coding: c.542C>T
MANE Select: NM_001031739
dbSNP: rs779282972
Type: single nucleotide variant
Location: chrX:15250456 (GRCh38)
Structure: AlphaFold pLDDT 91.89 · 4 PDB
Residue 181: an α-helix

Full ASB9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB9 p.Ala14Val Uncertain significance ★ ⚠ same type
ASB9 p.Ala215Gly Uncertain significance ★ same type
ASB9 p.Arg234Cys Uncertain significance ★ ⚠ same type
ASB9 p.Arg267Gln Uncertain significance ★ ⚠ same type
ASB9 p.Gln178Arg Uncertain significance ★ ⚠ same type
ASB9 p.Gln179His Uncertain significance ★ ⚠ same type
ASB9 p.Gln247Lys Uncertain significance ★ ⚠ same type
ASB9 p.Gln274Lys 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/asb9-p-ala181val (accessed [today's date]).

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