Is GLIS3 p.Pro307= (c.921G>A) pathogenic?

GLIS3 p.Pro307= (c.921G>A) is classified Likely benign in GLIS3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-16). Very rare (popmax 0.00988%, sas); Associated with Inborn genetic diseases.

What condition is associated with GLIS3 p.Pro307= (c.921G>A)?

GLIS3 p.Pro307= (c.921G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GLIS3 p.Pro307= (c.921G>A) in the general population?

GLIS3 p.Pro307= (c.921G>A) is very rare (popmax 0.00988%, sas) (gnomAD).

GLIS3 p.Pro307=

c.921G>A · VCV4620899

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Conditions

Inborn genetic diseases

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 -11	GERP -4.3
Overall
CADD	0.346	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00988% South Asian · 9/91,092 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.000805% 13/1,614,214 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,121
African / African-American	0.00266%	37,531
East Asian	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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: GLIS3
Protein: p.Pro307=
Coding: c.921G>A
MANE Select: NM_001042413
Type: single nucleotide variant
Location: chr9:4118557 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 49.95
Residue 307: the 'disordered' region

Full GLIS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GLIS3 p.Ala233Thr Uncertain significance ★★ ⚠ same condition
GLIS3 p.Ala784Pro Uncertain significance ★★ ⚠ same condition
GLIS3 p.Arg637Cys Uncertain significance ★★ ⚠ same condition
GLIS3 p.Arg663Gln Uncertain significance ★★ ⚠ same condition
GLIS3 p.Asp310Asn Uncertain significance ★★ ⚠ same condition
GLIS3 p.Cys676Phe Uncertain significance ★★ same condition
GLIS3 p.Gly385Ser Uncertain significance ★★ ⚠ same condition
GLIS3 p.Gly491Arg 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/glis3-p-pro307 (accessed [today's date]).

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