CRYAA p.Phe27=
c.81C>T · rs373635187 · VCV697528
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0116%, eas)
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 -3.6 | GERP -2.3 |
| Overall | ||
| CADD | 11.69 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0116%
East Asian · 5/43,016 alleles
Filtering AF
0.0045%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00326%
Overall
0.00413%
40/968,778 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0116% | 8,603 |
| European (non-Finnish) | 0.00513% | 19,490 |
| Remaining individualsnot grpmax-eligible | 0.00245% | 40,860 |
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.Phe27=
- Coding
- c.81C>T
- MANE Select
- NM_000394
- dbSNP
- rs373635187
- Type
- single nucleotide variant
- Location
- chr21:43169180 (GRCh38)
- Structure
- AlphaFold pLDDT 74.60 · 5 PDB
- Residue 27
- 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.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
- CRYAA p.Arg54Cys Pathogenic/Likely pathogenic ★★ same type
- CRYAA p.Gly98Arg 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-phe27 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown