Is CNNM2 p.Thr730= (c.2190C>T) pathogenic?

CNNM2 p.Thr730= (c.2190C>T) is classified Conflicting classifications of pathogenicity in CNNM2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-29). Rare (popmax 0.102%, eas); Associated with renal hypomagnesemia 6.

What condition is associated with CNNM2 p.Thr730= (c.2190C>T)?

CNNM2 p.Thr730= (c.2190C>T) is associated with renal hypomagnesemia 6 (ClinVar).

How common is CNNM2 p.Thr730= (c.2190C>T) in the general population?

CNNM2 p.Thr730= (c.2190C>T) is rare (popmax 0.102%, eas) (gnomAD).

CNNM2 p.Thr730=

c.2190C>T · rs1021927212 · VCV879849

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.102%, eas)

Conditions

renal hypomagnesemia 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor loss, 22 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.9	GERP 2.4, phastCons 1
Overall
CADD	10.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.102% East Asian · 46/44,892 alleles

Filtering AF 0.0789% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0706%

Overall 0.00291% 47/1,613,800 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.102%	976
Remaining individualsnot grpmax-eligible	0.0016%	62,458

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: CNNM2
Protein: p.Thr730=
Coding: c.2190C>T
MANE Select: NM_017649
dbSNP: rs1021927212
Type: single nucleotide variant
Location: chr10:103071796 (GRCh38)
Gene constraint: LOEUF 0.312 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.70 · 7 PDB

Full CNNM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

renal hypomagnesemia 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNNM2 p.Thr730Ala Uncertain significance ★ ⚠ same residue
CNNM2 p.Arg602Ter Likely pathogenic ★★ same condition
CNNM2 c.1904-6C>G Uncertain significance ★★ same condition
CNNM2 p.Ala45Glu Uncertain significance ★★ ⚠ same condition
CNNM2 p.Ala671Val Uncertain significance ★★ ⚠ same condition
CNNM2 p.Ala874Thr Uncertain significance ★★ ⚠ same condition
CNNM2 p.Ala92Thr Uncertain significance ★★ ⚠ same condition
CNNM2 p.Arg153His 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/cnnm2-p-thr730 (accessed [today's date]).

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