TYR p.Pro417=
c.1251C>T · rs1484196773 · VCV2108048
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00178%, 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 -0.08 | GERP 1.1, phastCons 0.66 |
| Overall | ||
| CADD | 6.358 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00178%
European (non-Finnish) · 21/1,178,624 alleles
Filtering AF
0.00114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000972%
Overall
0.00143%
23/1,611,914 alleles · very rare
exomes 21/1,460,056 · genomes 2/151,858 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00178% | 56,125 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,368 |
| African / African-American | 0.00134% | 74,768 |
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.Pro417=
- Coding
- c.1251C>T
- MANE Select
- NM_000372
- dbSNP
- rs1484196773
- Type
- single nucleotide variant
- Location
- chr11:89284839 (GRCh38)
- Gene constraint
- LOEUF 1.346 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.79 · 1 PDB
- Residue 417
- a UniProt-annotated variant site (in oca1a)
Similar variants
- 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
- TYR c.1037-3C>G Pathogenic/Likely pathogenic ★★ same type
- TYR c.1037-7T>A Pathogenic/Likely pathogenic ★★ same type
- TYR c.1185-2A>G Pathogenic/Likely pathogenic ★★ same type
- TYR c.1366+1G>T 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-pro417 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown