TYR p.Arg217=
c.651G>A · rs778827696 · VCV2060544
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.045%, sas)
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 0.6 | GERP 0.07, phastCons 0.49 |
| Overall | ||
| CADD | 5.604 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.045%
South Asian · 41/91,030 alleles
Filtering AF
0.0341%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0302%
Overall
0.0026%
42/1,612,652 alleles · ultra-rare
exomes 39/1,460,506 · genomes 3/152,146 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.045% | 2,220 |
| European (non-Finnish) | 8.48e-05% | 1,179,217 |
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.Arg217=
- Coding
- c.651G>A
- MANE Select
- NM_000372
- dbSNP
- rs778827696
- Type
- single nucleotide variant
- Location
- chr11:89178604 (GRCh38)
- Gene constraint
- LOEUF 1.346 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.79 · 1 PDB
- Residue 217
- a UniProt-annotated variant site (in oca1a)
Similar variants
- TYR p.Arg217Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
- TYR p.Arg217Gly Pathogenic ★ ⚠ same residue
- TYR p.Arg217Pro Likely pathogenic ★ same residue
- TYR p.Arg217Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
- TYR p.Arg217fs 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
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-arg217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown