TYR p.Cys91=
c.273C>T · rs2135242041 · VCV1674248
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
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 -0.44 | GERP -1.7, phastCons 0.004 |
| Overall | ||
| CADD | 6.53 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,024 alleles
Overall
6.2e-05%
1/1,614,172 alleles · very rare
exomes 1/1,461,866 · genomes 0/152,306 · joint denominator
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
- TYR
- Protein
- p.Cys91=
- Coding
- c.273C>T
- MANE Select
- NM_000372
- dbSNP
- rs2135242041
- Type
- single nucleotide variant
- Location
- chr11:89178226 (GRCh38)
- Gene constraint
- LOEUF 1.346 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.79 · 1 PDB
- Residue 91
- a UniProt-annotated variant site (in oca1a)
Similar variants
- TYR p.Cys91Ser Pathogenic/Likely pathogenic ★★ same residue
- TYR p.Cys91Tyr Pathogenic/Likely pathogenic ★★ same residue
- TYR p.Cys91Arg Likely pathogenic ★ same residue
- TYR p.Cys91Phe Likely pathogenic ★ same residue
- TYR c.1036+1G>A Pathogenic/Likely pathogenic ★★ same type
- TYR c.1036+2T>G Pathogenic ★★ same type
- TYR c.1037-1G>A Pathogenic/Likely pathogenic ★★ same type
- TYR c.1037-2A>G 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/tyr-p-cys91 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown