Is ASB2 p.Arg524Ser (c.1572G>T) pathogenic?

ASB2 p.Arg524Ser (c.1572G>T) is classified Uncertain significance in ASB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: ambiguous (0.4031); Rare (popmax 0.131%, afr).

How common is ASB2 p.Arg524Ser (c.1572G>T) in the general population?

ASB2 p.Arg524Ser (c.1572G>T) is rare (popmax 0.131%, afr) (gnomAD).

What do computational predictors say about ASB2 p.Arg524Ser (c.1572G>T)?

AlphaMissense predicts ambiguous (score 0.4031) — an in-silico prediction, not a clinical call.

ASB2 p.Arg524Ser

c.1572G>T · VCV3434818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4031 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.131%, afr)

Computational evidence

Protein change
AlphaMissense	0.4031	ambiguous
REVEL	0.237	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	phastCons 0.81
Regional constraint	o/e 1.05	unconstrained · MANE · 30 kb · p 0.18 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R476S vs ClinVar R524S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.131% African / African-American · 97/73,858 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.00646% 102/1,578,560 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.131%	761
Admixed American	0.00534%	18,739
Remaining individualsnot grpmax-eligible	0.00165%	60,754
European (non-Finnish)	8.63e-05%	1,158,700

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.Arg524Ser
Coding: c.1572G>T
MANE Select: NM_001202429
Type: single nucleotide variant
Location: chr14:93939153 (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-arg524ser (accessed [today's date]).

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