GRHL2 p.Pro144=
c.432C>T · rs756526962 · VCV666698
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 -4.8 | GERP -2.6 |
| Overall | ||
| CADD | 4.615 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,888 alleles
Filtering AF
0.00103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00083%
Overall
0.00136%
22/1,613,990 alleles · very rare
exomes 21/1,461,894 · genomes 1/152,096 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,888 |
| Admixed American | 0.00167% | 59,992 |
| European (non-Finnish) | 0.00161% | 62,107 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
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.Pro144=
- Coding
- c.432C>T
- MANE Select
- NM_024915
- dbSNP
- rs756526962
- Type
- single nucleotide variant
- Location
- chr8:101558566 (GRCh38)
- Gene constraint
- LOEUF 0.367 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.46 · 1 PDB
Similar variants
- 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
- GRHL2 p.Ala327Val 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-pro144 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown