Is ASB15 p.Cys511Arg (c.1531T>C) pathogenic?

ASB15 p.Cys511Arg (c.1531T>C) is classified Uncertain significance in ASB15 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-09). AlphaMissense: likely pathogenic (0.8935); Absent from gnomAD v4.1.

How common is ASB15 p.Cys511Arg (c.1531T>C) in the general population?

ASB15 p.Cys511Arg (c.1531T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASB15 p.Cys511Arg (c.1531T>C)?

AlphaMissense predicts likely pathogenic (score 0.8935) — an in-silico prediction, not a clinical call.

ASB15 p.Cys511Arg

c.1531T>C · rs2536023702 · VCV2260016

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8935 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8935	likely pathogenic · top 7% in ASB15
REVEL	0.789	moderately pathogenic-leaning
SaProt	LLR -10.61	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 22 kb · p 0.3 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASB15
Protein: p.Cys511Arg
Coding: c.1531T>C
MANE Select: NM_001290258
dbSNP: rs2536023702
Type: single nucleotide variant
Location: chr7:123630056 (GRCh38)
Gene constraint: LOEUF 1.186 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.39

Full ASB15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB15 p.Ala194Thr Uncertain significance ★ ⚠ same type
ASB15 p.Ala250Thr Uncertain significance ★ ⚠ same type
ASB15 p.Ala315Gly Uncertain significance ★ ⚠ same type
ASB15 p.Ala372Thr Uncertain significance ★ ⚠ same type
ASB15 p.Ala558Val Uncertain significance ★ ⚠ same type
ASB15 p.Ala568Pro Uncertain significance ★ ⚠ same type
ASB15 p.Ala72Ser Uncertain significance ★ ⚠ same type
ASB15 p.Ala72Val 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/asb15-p-cys511arg (accessed [today's date]).

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