Is ASB2 p.Ser345Pro (c.1033T>C) pathogenic?

ASB2 p.Ser345Pro (c.1033T>C) is classified Uncertain significance in ASB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely pathogenic (0.9715); Ultra-rare (popmax 0.0356%, eas).

How common is ASB2 p.Ser345Pro (c.1033T>C) in the general population?

ASB2 p.Ser345Pro (c.1033T>C) is ultra-rare (popmax 0.0356%, eas) (gnomAD).

What do computational predictors say about ASB2 p.Ser345Pro (c.1033T>C)?

AlphaMissense predicts likely pathogenic (score 0.9715) — an in-silico prediction, not a clinical call.

ASB2 p.Ser345Pro

c.1033T>C · rs771810059 · VCV3130159

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9715 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0356%, eas)

Computational evidence

Protein change
AlphaMissense	0.9715	likely pathogenic · top 9% in ASB2
REVEL	0.441	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.2	GERP -3.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 30 kb · p 0.18 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S297P vs ClinVar S345P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0356% East Asian · 16/44,892 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00105% 17/1,613,938 alleles · ultra-rare exomes 14/1,461,838 · genomes 3/152,100 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0356%	2,806
Admixed American	0.00167%	59,994

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: ASB2
Protein: p.Ser345Pro
Coding: c.1033T>C
MANE Select: NM_001202429
dbSNP: rs771810059
Type: single nucleotide variant
Location: chr14:93947368 (GRCh38)
Gene constraint: LOEUF 1.243 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.96

Full ASB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB2 p.Ala132Thr Uncertain significance ★ ⚠ same type
ASB2 p.Ala196Thr Uncertain significance ★ same type
ASB2 p.Ala212Asp Uncertain significance ★ ⚠ same type
ASB2 p.Ala229Thr Uncertain significance ★ same type
ASB2 p.Ala269Thr Uncertain significance ★ ⚠ same type
ASB2 p.Ala305Thr Uncertain significance ★ ⚠ same type
ASB2 p.Ala330Thr Uncertain significance ★ ⚠ same type
ASB2 p.Ala376Pro 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/asb2-p-ser345pro (accessed [today's date]).

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