Is CNNM4 c.*252G>C pathogenic?

CNNM4 c.252G>C is classified Uncertain significance in CNNM4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Absent from gnomAD v4.1; Associated with Jalili syndrome.

What condition is associated with CNNM4 c.*252G>C?

CNNM4 c.*252G>C is associated with Jalili syndrome (ClinVar).

How common is CNNM4 c.*252G>C in the general population?

CNNM4 c.*252G>C is absent from gnomAD v4.1 (gnomAD).

CNNM4 c.*252G>C

rs778510289 · VCV895115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Jalili syndrome

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 1.4	GERP -0.87, phastCons 1
Non-coding constraint	Z 2.78	1 kb window · o/e 0.81 · regional · uncalibrated
Overall
CADD	9.398	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CNNM4
Coding: c.*252G>C
MANE Select: NM_020184
dbSNP: rs778510289
Type: single nucleotide variant
Location: chr2:96809769 (GRCh38)
Gene constraint: LOEUF 0.794 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.20 · 6 PDB

Full CNNM4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

CNNM4 p.Arg519Ter Pathogenic ★★ same condition
CNNM4 p.Gln564Ter Pathogenic ★★ same condition
CNNM4 p.Gln717Ter Pathogenic/Likely pathogenic ★★ same condition
CNNM4 c.2130+5G>A Uncertain significance ★★ same condition
CNNM4 c.*1126G>A Uncertain significance ★★ same condition
CNNM4 p.Ala598Thr Uncertain significance ★★ ⚠ same condition
CNNM4 p.Arg523Gln Uncertain significance ★★ ⚠ same condition
CNNM4 p.Arg651Cys 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/cnnm4-c-star-252g-c (accessed [today's date]).

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