CRYAA p.Leu40=
c.118C>T · VCV4750561
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00651%, amr)
Conditions
1
cataract 9 multiple types
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 12.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00651%
Admixed American · 3/46,094 alleles
Filtering AF
0.00173%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000878%
Overall
0.000377%
3/795,296 alleles · very rare
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
- CRYAA
- Protein
- p.Leu40=
- Coding
- c.118C>T
- MANE Select
- NM_000394
- Type
- single nucleotide variant
- Location
- chr21:43169217 (GRCh38)
- Structure
- AlphaFold pLDDT 74.60 · 5 PDB
- Residue 40
- a UniProt-annotated variant site (in ctrct9; uncertain significance); the 'required for complex formation with bfsp1 and bfsp2; during homooligomerization, mediates the association of 2 dimers to form a tetramer' region
Similar variants
- CRYAA p.Leu40Pro Uncertain significance ★ ⚠ same residue
- CRYAA p.Arg116Cys Pathogenic ★★ same condition
- CRYAA p.Arg116His Pathogenic ★★ same condition
- CRYAA p.Arg12Cys Pathogenic/Likely pathogenic ★★ same condition
- CRYAA p.Arg21Gln Pathogenic ★★ ⚠ same condition
- CRYAA p.Arg21Trp Pathogenic/Likely pathogenic ★★ same condition
- CRYAA p.Arg54Cys Pathogenic/Likely pathogenic ★★ same condition
- CRYAA p.Gly98Arg Pathogenic ★★ 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/cryaa-p-leu40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown