Is GRHL3 p.Pro293= (c.879A>G) pathogenic?

GRHL3 p.Pro293= (c.879A>G) is classified Likely benign in GRHL3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-06). Very rare (popmax 0.00668%, afr); Associated with GRHL3-related disorder.

What condition is associated with GRHL3 p.Pro293= (c.879A>G)?

GRHL3 p.Pro293= (c.879A>G) is associated with GRHL3-related disorder (ClinVar).

How common is GRHL3 p.Pro293= (c.879A>G) in the general population?

GRHL3 p.Pro293= (c.879A>G) is very rare (popmax 0.00668%, afr) (gnomAD).

GRHL3 p.Pro293=

c.879A>G · rs149165410 · VCV3045146

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Conditions

GRHL3-related disorder

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 -20	GERP -3.7
Overall
CADD	0.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,880 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00031% 5/1,613,012 alleles · very rare exomes 2/1,460,786 · genomes 3/152,226 · joint denominator

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.Pro293=
Coding: c.879A>G
MANE Select: NM_198173
dbSNP: rs149165410
Type: single nucleotide variant
Location: chr1:24338030 (GRCh38)
Gene constraint: LOEUF 0.4 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.27
Residue 293: the grh/cp2 db domain

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

Disease context

GRHL3-related disorder

Similar variants

STPG1 p.Asn293Asp Uncertain significance ★ ⚠ same residue
STPG1 p.Asn293Ser Uncertain significance ★ ⚠ same residue
GRHL3 p.Pro39Leu Uncertain significance ★★ ⚠ same condition
GRHL3 p.Glu498Ter Likely pathogenic ★ same condition
GRHL3 p.Arg313Pro Uncertain significance ★ ⚠ same condition
GRHL3 p.Asp288His Uncertain significance ★ ⚠ same condition
GRHL3 p.His464Gln Uncertain significance ★ ⚠ same condition
GRHL3 p.Met570Val Uncertain significance ★ 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-pro293 (accessed [today's date]).

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