Is GLIS3 p.Arg780= (c.2340G>C) pathogenic?

GLIS3 p.Arg780= (c.2340G>C) is classified Likely benign in GLIS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). Very rare (popmax 8.47e-05%, nfe).

How common is GLIS3 p.Arg780= (c.2340G>C) in the general population?

GLIS3 p.Arg780= (c.2340G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

GLIS3 p.Arg780=

c.2340G>C · VCV3623095

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 1	GERP 1.7, phastCons 1
Overall
CADD	7.781	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,010 alleles

Overall 6.2e-05% 1/1,614,090 alleles · very rare exomes 1/1,461,830 · genomes 0/152,260 · 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.Arg780=
Coding: c.2340G>C
MANE Select: NM_001042413
Type: single nucleotide variant
Location: chr9:3856142 (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 p.Arg780Gln Uncertain significance ★★ ⚠ same residue
GLIS3 p.Arg780Gly Uncertain significance ★ ⚠ same residue
GLIS3 p.Arg780Trp Uncertain significance ★ ⚠ same residue
GLIS3 p.Arg780fs Pathogenic same residue
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

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-arg780 (accessed [today's date]).

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