Is CNNM2 p.Ser800= (c.2400G>A) pathogenic?

CNNM2 p.Ser800= (c.2400G>A) is classified Conflicting classifications of pathogenicity in CNNM2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-05-06). Very rare (popmax 0.00885%, nfe); Associated with renal hypomagnesemia 6.

What condition is associated with CNNM2 p.Ser800= (c.2400G>A)?

CNNM2 p.Ser800= (c.2400G>A) is associated with renal hypomagnesemia 6 (ClinVar).

How common is CNNM2 p.Ser800= (c.2400G>A) in the general population?

CNNM2 p.Ser800= (c.2400G>A) is very rare (popmax 0.00885%, nfe) (gnomAD).

CNNM2 p.Ser800=

c.2400G>A · rs775113694 · VCV877907

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00885%, nfe)

Conditions

renal hypomagnesemia 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.7	GERP -4.8
Overall
CADD	2.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00885% European (non-Finnish) · 102/1,152,038 alleles

Filtering AF 0.00742% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00692%

Overall 0.00743% 116/1,560,542 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00885%	11,294
Remaining individualsnot grpmax-eligible	0.00826%	12,110
Admixed American	0.00773%	12,939
East Asian	0.00719%	13,912
African / African-American	0.00136%	73,432
South Asian	0.00118%	84,606

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.Ser800=
Coding: c.2400G>A
MANE Select: NM_017649
dbSNP: rs775113694
Type: single nucleotide variant
Location: chr10:103076252 (GRCh38)
Gene constraint: LOEUF 0.312 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.70 · 7 PDB
Residue 800: a β-strand

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.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
CNNM2 p.Arg30Cys 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-ser800 (accessed [today's date]).

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