GRHL2 p.Pro472=
c.1416T>C · rs371708806 · VCV227416
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0151%, 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 -12 | GERP -5.3 |
| Overall | ||
| CADD | 1.368 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0151%
European (non-Finnish) · 178/1,179,904 alleles
Filtering AF
0.0132%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0125%
Overall
0.0118%
190/1,613,900 alleles · ultra-rare
exomes 177/1,461,720 · genomes 13/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0151% | 6,629 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,925 |
| African / African-American | 0.004% | 24,974 |
| South Asian | 0.0022% | 45,543 |
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.Pro472=
- Coding
- c.1416T>C
- MANE Select
- NM_024915
- dbSNP
- rs371708806
- Type
- single nucleotide variant
- Location
- chr8:101632296 (GRCh38)
- Gene constraint
- LOEUF 0.367 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.46 · 1 PDB
- Residue 472
- the grh/cp2 db domain
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-pro472 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown