TYR p.Arg43=
c.129G>A · rs377546778 · VCV2081660
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0186%, nfe)
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 -0.2 | GERP -1.9, phastCons 0.045 |
| Overall | ||
| CADD | 3.565 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0186%
European (non-Finnish) · 220/1,180,026 alleles
Filtering AF
0.0166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0158%
Overall
0.0141%
227/1,614,178 alleles · ultra-rare
exomes 214/1,461,876 · genomes 13/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0186% | 5,364 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,502 |
| African / African-American | 0.00266% | 37,525 |
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.Arg43=
- Coding
- c.129G>A
- MANE Select
- NM_000372
- dbSNP
- rs377546778
- Type
- single nucleotide variant
- Location
- chr11:89178082 (GRCh38)
- Gene constraint
- LOEUF 1.346 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.79 · 1 PDB
Similar variants
- TYR p.Arg43Gly Likely benign ★ 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-arg43 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown