GRHL2 p.Ser217=
c.651C>T · rs34332949 · VCV46220
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.4%, 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 -3.1 | GERP 1.5 |
| Overall | ||
| CADD | 10.28 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.4%
African / African-American · 3,297/75,008 alleles
Filtering AF
4.27%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.22%
Overall
0.23%
3,708/1,614,042 alleles · low-frequency
exomes 1,813/1,461,778 · genomes 1,895/152,264 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.4% | 23 |
| Remaining individualsnot grpmax-eligible | 0.282% | 355 |
| Admixed American | 0.278% | 359 |
| Middle Eastern | 0.0825% | 1,212 |
| South Asian | 0.011% | 9,108 |
| European (non-Finnish) | 0.00449% | 22,264 |
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.Ser217=
- Coding
- c.651C>T
- MANE Select
- NM_024915
- dbSNP
- rs34332949
- Type
- single nucleotide variant
- Location
- chr8:101558785 (GRCh38)
- Gene constraint
- LOEUF 0.367 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.46 · 1 PDB
Similar variants
- GRHL2 p.Ser217Arg 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-ser217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown