Is ASB2 p.Arg234Cys (c.700C>T) pathogenic?

ASB2 p.Arg234Cys (c.700C>T) is classified Uncertain significance in ASB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: ambiguous (0.508); Very rare (popmax 0.0022%, sas).

How common is ASB2 p.Arg234Cys (c.700C>T) in the general population?

ASB2 p.Arg234Cys (c.700C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about ASB2 p.Arg234Cys (c.700C>T)?

AlphaMissense predicts ambiguous (score 0.508) — an in-silico prediction, not a clinical call.

ASB2 p.Arg234Cys

c.700C>T · VCV4152531

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.508 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Computational evidence

Protein change
AlphaMissense	0.508	ambiguous
REVEL	0.661	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 30 kb · p 0.18 · regional, not allelic
Overall
CADD	28.0	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 R186C vs ClinVar R234C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,088 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00118% 19/1,613,654 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,825
South Asiangrpmax	0.0022%	45,544
European (non-Finnish)	0.00119%	84,282

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg234Cys
Coding: c.700C>T
MANE Select: NM_001202429
Type: single nucleotide variant
Location: chr14:93951179 (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.Arg234His Uncertain significance ★ same residue
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

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-arg234cys (accessed [today's date]).

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