Is CNNM2 p.Arg797Ter (c.2389C>T) pathogenic?

CNNM2 p.Arg797Ter (c.2389C>T) is classified Conflicting classifications of pathogenicity in CNNM2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-03-17). Absent from gnomAD v4.1; Associated with hypomagnesemia, seizures, and intellectual disability 1.

What condition is associated with CNNM2 p.Arg797Ter (c.2389C>T)?

CNNM2 p.Arg797Ter (c.2389C>T) is associated with hypomagnesemia, seizures, and intellectual disability 1 (ClinVar).

How common is CNNM2 p.Arg797Ter (c.2389C>T) in the general population?

CNNM2 p.Arg797Ter (c.2389C>T) is absent from gnomAD v4.1 (gnomAD).

CNNM2 p.Arg797Ter

c.2389C>T · rs2065688398 · VCV996055

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,564,632)

Conditions

hypomagnesemia, seizures, and intellectual disability 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (7 of 8, 29 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.87 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.8	GERP 0.5, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,564,632). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CNNM2
Protein: p.Arg797Ter
Coding: c.2389C>T
MANE Select: NM_017649
dbSNP: rs2065688398
Type: single nucleotide variant
Location: chr10:103076241 (GRCh38)
Gene constraint: LOEUF 0.312 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.70 · 7 PDB
Residue 797: a β-strand

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

Disease context

hypomagnesemia, seizures, and intellectual disability 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNNM2 p.Arg797Gln Uncertain significance ★ ⚠ same residue
CNNM2 p.Arg602Ter Likely pathogenic ★★ same condition
CNNM2 p.Glu122Lys Pathogenic/Likely pathogenic ★★ same condition
CNNM2 p.Glu357Lys Pathogenic ★★ same condition
CNNM2 p.Ser269Trp Pathogenic/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

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-arg797ter (accessed [today's date]).

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