Is CNNM2 p.Asp848= (c.2544C>T) pathogenic?

CNNM2 p.Asp848= (c.2544C>T) is classified Benign in CNNM2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-05). Common (popmax 15.4%, mid) — too common for a highly-penetrant pathogenic allele; Associated with renal hypomagnesemia 6.

What condition is associated with CNNM2 p.Asp848= (c.2544C>T)?

CNNM2 p.Asp848= (c.2544C>T) is associated with renal hypomagnesemia 6 (ClinVar).

CNNM2 p.Asp848=

Q: How common is CNNM2 p.Asp848= (c.2544C>T) in the general population?

CNNM2 p.Asp848= (c.2544C>T) is common (popmax 15.4%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2544C>T · rs35647154 · VCV298650

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 15.4%, mid) — too common for a highly-penetrant pathogenic allele

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 -3.2	GERP -4.5
Overall
CADD	7.554	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.4% Middle Eastern · 931/6,058 alleles

Filtering AF 14.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.2%

Overall 6.14% 99,094/1,613,908 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	15.4%	7
Ashkenazi Jewishnot grpmax-eligible	8.72%	11
Amishnot grpmax-eligible	8%	12
European (non-Finnish)	6.86%	15
Remaining individualsnot grpmax-eligible	6.16%	16
Finnishnot grpmax-eligible	5.62%	18
Admixed American	4.58%	22
South Asian	2.74%	36
African / African-American	2.46%	41
East Asian	0.0134%	7,482

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.Asp848=
Coding: c.2544C>T
MANE Select: NM_017649
dbSNP: rs35647154
Type: single nucleotide variant
Location: chr10:103077096 (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.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-asp848 (accessed [today's date]).

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