GRHL2 p.Tyr139=
c.417C>T · rs768143303 · VCV681159
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, afr)
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 -0.065 | GERP 1.4, phastCons 0.67 |
| Overall | ||
| CADD | 2.233 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
African / African-American · 10/74,894 alleles
Filtering AF
0.00723%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0055%
Overall
0.00143%
23/1,614,024 alleles · ultra-rare
exomes 22/1,461,892 · genomes 1/152,132 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0134% | 7,489 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,927 |
| South Asian | 0.0022% | 45,529 |
| European (non-Finnish) | 0.000339% | 295,010 |
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
- GRHL2
- Protein
- p.Tyr139=
- Coding
- c.417C>T
- MANE Select
- NM_024915
- dbSNP
- rs768143303
- Type
- single nucleotide variant
- Location
- chr8:101558551 (GRCh38)
- Gene constraint
- LOEUF 0.367 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.46 · 1 PDB
Similar variants
- GRHL2 p.Tyr139His Uncertain significance ★ ⚠ same residue
- GRHL2 p.Arg290Ter Pathogenic/Likely pathogenic ★★ same type
- GRHL2 p.Arg426Ter Pathogenic/Likely pathogenic ★★ same type
- GRHL2 p.Arg75Ter Pathogenic ★★ same type
- GRHL2 c.1486-10T>G Uncertain significance ★★ same type
- GRHL2 p.Ala148Thr Uncertain significance ★★ ⚠ same type
- GRHL2 p.Ala198Thr Uncertain significance ★★ ⚠ same type
- GRHL2 p.Ala28Gly Uncertain significance ★★ ⚠ 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/grhl2-p-tyr139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown