Is ASB5 p.Val96Ile (c.286G>A) pathogenic?

ASB5 p.Val96Ile (c.286G>A) is classified Uncertain significance in ASB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely benign (0.1113); Very rare (popmax 0.00017%, nfe).

How common is ASB5 p.Val96Ile (c.286G>A) in the general population?

ASB5 p.Val96Ile (c.286G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about ASB5 p.Val96Ile (c.286G>A)?

AlphaMissense predicts likely benign (score 0.1113) — an in-silico prediction, not a clinical call.

ASB5 p.Val96Ile

c.286G>A · rs575382169 · VCV2254399

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1113 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1113	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -9.25	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 7.7	GERP 2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 54 kb · p 0.91 · regional, not allelic
Overall
CADD	24.5	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 0.00017% European (non-Finnish) · 2/1,178,730 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,459,740 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: ASB5
Protein: p.Val96Ile
Coding: c.286G>A
MANE Select: NM_080874
dbSNP: rs575382169
Type: single nucleotide variant
Location: chr4:176222411 (GRCh38)
Gene constraint: LOEUF 1.317 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.93

Full ASB5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB5 p.Ala175Thr Uncertain significance ★ ⚠ same type
ASB5 p.Ala176Ser Uncertain significance ★ ⚠ same type
ASB5 p.Ala51Pro Uncertain significance ★ ⚠ same type
ASB5 p.Ala69Val Uncertain significance ★ ⚠ same type
ASB5 p.Ala77Ser Uncertain significance ★ ⚠ same type
ASB5 p.Ala85Thr Uncertain significance ★ ⚠ same type
ASB5 p.Arg302Gln Uncertain significance ★ ⚠ same type
ASB5 p.Asn142Lys 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/asb5-p-val96ile (accessed [today's date]).

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