Is GLIS3 p.Pro730= (c.2190C>T) pathogenic?

GLIS3 p.Pro730= (c.2190C>T) is classified Likely benign in GLIS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). Very rare (popmax 0.00167%, amr).

How common is GLIS3 p.Pro730= (c.2190C>T) in the general population?

GLIS3 p.Pro730= (c.2190C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

GLIS3 p.Pro730=

c.2190C>T · rs772656744 · VCV3023684

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Overall
CADD	11.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,010 alleles

Overall 6.2e-05% 1/1,614,080 alleles · very rare exomes 1/1,461,836 · genomes 0/152,244 · 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: GLIS3
Protein: p.Pro730=
Coding: c.2190C>T
MANE Select: NM_001042413
dbSNP: rs772656744
Type: single nucleotide variant
Location: chr9:3879534 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 49.95

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

Similar variants

GLIS3 c.596+6A>C Uncertain significance ★★ same type
GLIS3 c.*3330G>A Uncertain significance ★★ same type
GLIS3 c.*3344T>A Uncertain significance ★★ same type
GLIS3 c.*3920G>A Uncertain significance ★★ same type
GLIS3 c.*69T>C Uncertain significance ★★ same type
GLIS3 p.Ala233Thr Uncertain significance ★★ ⚠ same type
GLIS3 p.Ala446Val Uncertain significance ★★ ⚠ same type
GLIS3 p.Ala615Ser 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/glis3-p-pro730 (accessed [today's date]).

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