Is GLIS2 p.Pro337= (c.1011G>A) pathogenic?

GLIS2 p.Pro337= (c.1011G>A) is classified Benign/Likely benign in GLIS2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-26). Low-frequency (popmax 4.86%, eas); Associated with nephronophthisis.

What condition is associated with GLIS2 p.Pro337= (c.1011G>A)?

GLIS2 p.Pro337= (c.1011G>A) is associated with nephronophthisis, kidney disorder, nephronophthisis 7 (ClinVar).

How common is GLIS2 p.Pro337= (c.1011G>A) in the general population?

GLIS2 p.Pro337= (c.1011G>A) is low-frequency (popmax 4.86%, eas) (gnomAD).

How is Nephronophthisis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

GLIS2 p.Pro337=

c.1011G>A · rs200814551 · VCV319216

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.86%, eas)

Conditions

nephronophthisis

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 -4	GERP -3.7
Overall
CADD	0.171	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.86% East Asian · 2,176/44,752 alleles

Filtering AF 4.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.62%

Overall 0.16% 2,579/1,610,730 alleles · low-frequency exomes 2,220/1,458,426 · genomes 359/152,304 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	4.86%	21
Remaining individualsnot grpmax-eligible	0.294%	341
South Asian	0.151%	663
Admixed American	0.0384%	2,602
Middle Eastern	0.033%	3,028
African / African-American	0.016%	6,250
European (non-Finnish)	0.0039%	25,638

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: GLIS2
Protein: p.Pro337=
Coding: c.1011G>A
MANE Select: NM_032575
dbSNP: rs200814551
Type: single nucleotide variant
Location: chr16:4336960 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI 0.33 (gnomAD)
Structure: AlphaFold pLDDT 55.47

Full GLIS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: kidney disorder nephronophthisis 7

For Nephronophthisis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

GLIS2 p.Pro337Leu Benign/Likely benign ★★ same residue
GLIS2 c.*1826C>T Uncertain significance ★★ same condition
GLIS2 c.*916G>A Uncertain significance ★★ same condition
GLIS2 p.Ala19Val Uncertain significance ★★ ⚠ same condition
GLIS2 p.Ala210Thr Uncertain significance ★★ same condition
GLIS2 p.Ala360Thr Uncertain significance ★★ ⚠ same condition
GLIS2 p.Ala437Thr Uncertain significance ★★ ⚠ same condition
GLIS2 p.Arg102Cys 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/glis2-p-pro337 (accessed [today's date]).

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