Is CRYAB p.Arg11Cys (c.31C>T) pathogenic?

CRYAB p.Arg11Cys (c.31C>T) is classified Uncertain significance in CRYAB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-18). AlphaMissense: likely pathogenic (0.6478); Very rare (popmax 0.00668%, afr); Associated with Cardiovascular phenotype.

What condition is associated with CRYAB p.Arg11Cys (c.31C>T)?

CRYAB p.Arg11Cys (c.31C>T) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1II (ClinVar).

How common is CRYAB p.Arg11Cys (c.31C>T) in the general population?

CRYAB p.Arg11Cys (c.31C>T) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about CRYAB p.Arg11Cys (c.31C>T)?

AlphaMissense predicts likely pathogenic (score 0.6478) — an in-silico prediction, not a clinical call.

CRYAB p.Arg11Cys

c.31C>T · rs781902168 · VCV222531

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6478 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.6478	likely pathogenic
REVEL	0.838	moderately pathogenic-leaning
SaProt	LLR -10.89	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 12	GERP 1.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,286 bp · p 0.3 · regional, not allelic
Overall
CADD	34.0	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

Grpmax group 0.00668% African / African-American · 5/74,892 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00113% 18/1,597,276 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,978
South Asian	0.00453%	22,081
Admixed American	0.00352%	28,421
East Asian	0.00225%	44,370
European (non-Finnish)	0.000512%	195,353

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: CRYAB
Protein: p.Arg11Cys
Coding: c.31C>T
MANE Select: NM_001289808
dbSNP: rs781902168
Type: single nucleotide variant
Location: chr11:111911694 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 21 PDB

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1II

Similar variants

CRYAB p.Arg11Gly Uncertain significance ★★ ⚠ same residue
CRYAB p.Arg11His Conflicting classifications of pathogenicity ★ ⚠ same residue
CRYAB p.Arg11Pro Uncertain significance ★ ⚠ same residue
CRYAB p.Arg11= Likely benign ★ same residue
CRYAB p.Arg11fs Pathogenic ★ same residue
CRYAB c.324+4T>A Uncertain significance ★★ same condition
CRYAB c.324+5G>T Uncertain significance ★★ same condition
CRYAB c.325-1G>A Uncertain significance ★★ same condition

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/cryab-p-arg11cys (accessed [today's date]).

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