Is ASB2 p.Ser101Tyr (c.302C>A) pathogenic?

ASB2 p.Ser101Tyr (c.302C>A) is classified Uncertain significance in ASB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). AlphaMissense: likely benign (0.1384); Very rare (popmax 0.005%, amr).

How common is ASB2 p.Ser101Tyr (c.302C>A) in the general population?

ASB2 p.Ser101Tyr (c.302C>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ASB2 p.Ser101Tyr (c.302C>A)?

AlphaMissense predicts likely benign (score 0.1384) — an in-silico prediction, not a clinical call.

ASB2 p.Ser101Tyr

c.302C>A · VCV3951351

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1384 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1384	likely benign
REVEL	0.169	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP -0.25, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 30 kb · p 0.18 · regional, not allelic
Overall
CADD	20.6	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S53Y vs ClinVar S101Y) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,036 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000616% 9/1,461,856 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,012
Finnishnot grpmax-eligible	0.00156%	64,020
European (non-Finnish)	0.000424%	236,005

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.Ser101Tyr
Coding: c.302C>A
MANE Select: NM_001202429
Type: single nucleotide variant
Location: chr14:93956775 (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-ser101tyr (accessed [today's date]).

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