Is ASB11 p.Pro68Ser (c.202C>T) pathogenic?

ASB11 p.Pro68Ser (c.202C>T) is classified Uncertain significance in ASB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: ambiguous (0.3612); Ultra-rare (popmax 0.0131%, amr).

How common is ASB11 p.Pro68Ser (c.202C>T) in the general population?

ASB11 p.Pro68Ser (c.202C>T) is ultra-rare (popmax 0.0131%, amr) (gnomAD).

What do computational predictors say about ASB11 p.Pro68Ser (c.202C>T)?

AlphaMissense predicts ambiguous (score 0.3612) — an in-silico prediction, not a clinical call.

ASB11 p.Pro68Ser

c.202C>T · VCV3788294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3612 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0131%, amr)

Computational evidence

Protein change
AlphaMissense	0.3612	ambiguous
REVEL	0.417	indeterminate
SaProt	LLR -11.36	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 32 kb · p 0.9 · regional, not allelic
Overall
CADD	24.6	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 0.0131% Admixed American · 6/45,666 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00389%

Overall 0.00091% 11/1,208,750 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0131%	7,611
African / African-American	0.00876%	11,411

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: ASB11
Protein: p.Pro68Ser
Coding: c.202C>T
MANE Select: NM_080873
Type: single nucleotide variant
Location: chrX:15302787 (GRCh38)
Structure: AlphaFold pLDDT 87.28 · 1 PDB
Residue 68: an α-helix

Full ASB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB11 p.Arg256His Uncertain significance ★★ ⚠ same type
ASB11 p.Arg208Trp Benign ★★ ⚠ same type
ASB11 p.Asp249Asn Benign ★★ same type
ASB11 p.Ala114Gly Uncertain significance ★ same type
ASB11 p.Ala145Thr Uncertain significance ★ ⚠ same type
ASB11 p.Ala259Gly Uncertain significance ★ ⚠ same type
ASB11 p.Ala268Val Uncertain significance ★ ⚠ same type
ASB11 p.Arg281Cys 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/asb11-p-pro68ser (accessed [today's date]).

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