Is CNNM2 p.Asn855= (c.2565C>T) pathogenic?

CNNM2 p.Asn855= (c.2565C>T) is classified Benign/Likely benign in CNNM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-05-05). Low-frequency (popmax 1.67%, sas); Associated with renal hypomagnesemia 6.

What condition is associated with CNNM2 p.Asn855= (c.2565C>T)?

CNNM2 p.Asn855= (c.2565C>T) is associated with renal hypomagnesemia 6, hypomagnesemia, seizures, and intellectual disability 1 (ClinVar).

How common is CNNM2 p.Asn855= (c.2565C>T) in the general population?

CNNM2 p.Asn855= (c.2565C>T) is low-frequency (popmax 1.67%, sas) (gnomAD).

CNNM2 p.Asn855=

c.2565C>T · rs540196504 · VCV722958

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.67%, sas)

Conditions

renal hypomagnesemia 6

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 -7.1	GERP -4.5
Overall
CADD	0.462	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.67% South Asian · 1,518/91,088 alleles

Filtering AF 1.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.57%

Overall 0.101% 1,630/1,613,988 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.67%	60
Remaining individualsnot grpmax-eligible	0.106%	947
Middle Eastern	0.0495%	2,019
East Asian	0.00668%	14,963
Admixed American	0.005%	20,010
African / African-American	0.004%	25,021
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.0028%	35,754

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.Asn855=
Coding: c.2565C>T
MANE Select: NM_017649
dbSNP: rs540196504
Type: single nucleotide variant
Location: chr10:103077117 (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

Also linked: hypomagnesemia, seizures, and intellectual disability 1

Similar variants

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
CNNM2 p.Ala874Thr 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-asn855 (accessed [today's date]).

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