Is GRHL3 p.Pro202= (c.606A>T) pathogenic?

GRHL3 p.Pro202= (c.606A>T) is classified Benign/Likely benign in GRHL3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-19). Rare (popmax 0.102%, nfe); Associated with van der Woude syndrome 2.

What condition is associated with GRHL3 p.Pro202= (c.606A>T)?

GRHL3 p.Pro202= (c.606A>T) is associated with van der Woude syndrome 2 (ClinVar).

How common is GRHL3 p.Pro202= (c.606A>T) in the general population?

GRHL3 p.Pro202= (c.606A>T) is rare (popmax 0.102%, nfe) (gnomAD).

GRHL3 p.Pro202=

c.606A>T · rs144957254 · VCV702796

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.102%, nfe)

Conditions

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 -3.9	GERP -3.7
Overall
CADD	2.286	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.102% European (non-Finnish) · 1,197/1,171,266 alleles

Filtering AF 0.0974% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0954%

Overall 0.0846% 1,353/1,600,020 alleles · rare exomes 1,282/1,447,702 · genomes 71/152,318 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.102%	979
Finnishnot grpmax-eligible	0.0758%	1,320
South Asian	0.0526%	1,900
Remaining individualsnot grpmax-eligible	0.0517%	1,935
Admixed American	0.022%	4,543
African / African-American	0.0214%	4,674

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.Pro202=
Coding: c.606A>T
MANE Select: NM_198173
dbSNP: rs144957254
Type: single nucleotide variant
Location: chr1:24336821 (GRCh38)
Gene constraint: LOEUF 0.4 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.27

Full GRHL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

van der Woude syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
GRHL3 c.686+13C>T 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-pro202 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown