GRHL3 p.Pro39=
c.117G>A · rs142785065 · VCV2200179
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
Conditions
1
van der Woude syndrome 2
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 -0.42 | GERP -2.7 |
| Overall | ||
| CADD | 10.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,084 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00241%
Overall
0.00198%
32/1,614,012 alleles · ultra-rare
exomes 28/1,461,840 · genomes 4/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| African / African-American | 0.00667% | 14,982 |
| South Asian | 0.00439% | 22,771 |
| European (non-Finnish) | 0.00178% | 56,191 |
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
- GRHL3
- Protein
- p.Pro39=
- Coding
- c.117G>A
- MANE Select
- NM_198173
- dbSNP
- rs142785065
- Type
- single nucleotide variant
- Location
- chr1:24331525 (GRCh38)
- Gene constraint
- LOEUF 0.4 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 61.27
- Residue 39
- the 'transcription activation' region
Similar variants
- GRHL3 p.Pro39Leu Uncertain significance ★★ ⚠ same residue
- GRHL3 p.Arg391Cys Pathogenic/Likely pathogenic ★★ same condition
- GRHL3 p.Arg264Trp Uncertain significance ★★ ⚠ same condition
- GRHL3 p.Arg417Gln Uncertain significance ★★ ⚠ same condition
- GRHL3 p.Arg490Cys Uncertain significance ★★ ⚠ same condition
- GRHL3 p.Pro147Ser Uncertain significance ★★ ⚠ same condition
- GRHL3 p.Trp602Ter Uncertain significance ★★ same condition
- GRHL3 c.204+13C>G Benign/Likely benign ★★ same condition
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/grhl3-p-pro39 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown