Is ASB9 p.Pro255Ser (c.763C>T) pathogenic?

ASB9 p.Pro255Ser (c.763C>T) is classified Uncertain significance in ASB9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely benign (0.1763); Very rare (popmax 0.000112%, nfe).

How common is ASB9 p.Pro255Ser (c.763C>T) in the general population?

ASB9 p.Pro255Ser (c.763C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about ASB9 p.Pro255Ser (c.763C>T)?

AlphaMissense predicts likely benign (score 0.1763) — an in-silico prediction, not a clinical call.

ASB9 p.Pro255Ser

c.763C>T · VCV3788928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1763 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1763	likely benign
REVEL	0.435	indeterminate
SaProt	LLR -10.97	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.38 · regional, not allelic
Overall
CADD	24.2	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 0.000112% European (non-Finnish) · 1/889,797 alleles

Overall 9.17e-05% 1/1,090,190 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: ASB9
Protein: p.Pro255Ser
Coding: c.763C>T
MANE Select: NM_001031739
Type: single nucleotide variant
Location: chrX:15244628 (GRCh38)
Structure: AlphaFold pLDDT 91.89 · 4 PDB
Residue 255: an α-helix; the socs box domain

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.Ala181Val 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

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-pro255ser (accessed [today's date]).

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