GRHL2 p.Val384=
c.1152G>A · rs776545912 · VCV682344
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0178%, eas)
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 5.1 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 12.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0178%
East Asian · 8/44,828 alleles
Filtering AF
0.00884%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00641%
Overall
0.000558%
9/1,613,398 alleles · ultra-rare
exomes 7/1,461,240 · genomes 2/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0178% | 5,603 |
| European (non-Finnish) | 8.48e-05% | 1,179,555 |
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.Val384=
- Coding
- c.1152G>A
- MANE Select
- NM_024915
- dbSNP
- rs776545912
- Type
- single nucleotide variant
- Location
- chr8:101619592 (GRCh38)
- Gene constraint
- LOEUF 0.367 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.46 · 1 PDB
- Residue 384
- 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-val384 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown