TYR p.Phe124=
c.372C>T · rs935942144 · VCV2991113
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00769%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -3.8, phastCons 0.001 |
| Overall | ||
| CADD | 5.402 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00769%
South Asian · 7/91,080 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00255%
Overall
0.00124%
20/1,614,046 alleles · very rare
exomes 15/1,461,886 · genomes 5/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00769% | 13,011 |
| African / African-American | 0.004% | 24,975 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| East Asian | 0.00223% | 44,874 |
| European (non-Finnish) | 0.000678% | 147,505 |
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.Phe124=
- Coding
- c.372C>T
- MANE Select
- NM_000372
- dbSNP
- rs935942144
- Type
- single nucleotide variant
- Location
- chr11:89178325 (GRCh38)
- Gene constraint
- LOEUF 1.346 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.79 · 1 PDB
Similar variants
- TYR p.Phe124Leu Uncertain significance ★ 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
- 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
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-phe124 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown