Is ASB5 p.Asn263Ile (c.788A>T) pathogenic?

ASB5 p.Asn263Ile (c.788A>T) is classified Uncertain significance in ASB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely pathogenic (0.9619); Absent from gnomAD v4.1.

How common is ASB5 p.Asn263Ile (c.788A>T) in the general population?

ASB5 p.Asn263Ile (c.788A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASB5 p.Asn263Ile (c.788A>T)?

AlphaMissense predicts likely pathogenic (score 0.9619) — an in-silico prediction, not a clinical call.

ASB5 p.Asn263Ile

c.788A>T · rs2477948978 · VCV2491541

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9619 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9619	likely pathogenic · top 9% in ASB5
REVEL	0.668	pathogenic-leaning
SaProt	LLR -15.60	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 54 kb · p 0.91 · regional, not allelic
Overall
CADD	26.1	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

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: ASB5
Protein: p.Asn263Ile
Coding: c.788A>T
MANE Select: NM_080874
dbSNP: rs2477948978
Type: single nucleotide variant
Location: chr4:176216892 (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-asn263ile (accessed [today's date]).

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