CRYAA p.Arg112Cys
c.334C>T · VCV4656854
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9971 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9971 | likely pathogenic · top 5% in CRYAA |
|---|---|---|
| REVEL | 0.894 | moderately pathogenic-leaning |
| SaProt | LLR -9.27 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.6 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.13 | constrained · MANE · 3,177 bp · p 1.9e-11 · regional, not allelic |
| Overall | ||
| CADD | 31.0 | PHRED · no single calibrated threshold — expert panels disagree |
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
- CRYAA
- Protein
- p.Arg112Cys
- Coding
- c.334C>T
- MANE Select
- NM_000394
- Type
- single nucleotide variant
- Location
- chr21:43172092 (GRCh38)
- Structure
- AlphaFold pLDDT 74.60 · 5 PDB
- Residue 112
- a UniProt-annotated variant site (in ctrct9; uncertain significance); the shsp domain
Similar variants
- CRYAA p.Arg112His Uncertain significance ★★ ⚠ same residue
- CRYAA p.Arg112Gly Uncertain significance ★ same residue
- CRYAA p.Arg116Cys Pathogenic ★★ same type
- CRYAA p.Arg116His Pathogenic ★★ same type
- CRYAA p.Arg116Ser Pathogenic ★★ same type
- CRYAA p.Arg12Cys Pathogenic/Likely pathogenic ★★ same type
- CRYAA p.Arg21Gln Pathogenic ★★ ⚠ same type
- CRYAA p.Arg21Trp Pathogenic/Likely pathogenic ★★ 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/cryaa-p-arg112cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown