Is CNNM2 p.Ser188= (c.564C>T) pathogenic?

CNNM2 p.Ser188= (c.564C>T) is classified Benign/Likely benign in CNNM2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-05). Rare (popmax 0.694%, nfe); Associated with renal hypomagnesemia 6.

What condition is associated with CNNM2 p.Ser188= (c.564C>T)?

CNNM2 p.Ser188= (c.564C>T) is associated with renal hypomagnesemia 6 (ClinVar).

How common is CNNM2 p.Ser188= (c.564C>T) in the general population?

CNNM2 p.Ser188= (c.564C>T) is rare (popmax 0.694%, nfe) (gnomAD).

CNNM2 p.Ser188=

c.564C>T · rs117691462 · VCV298638

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.694%, nfe)

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 1.1	GERP -0.79, phastCons 1
Overall
CADD	12.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.694% European (non-Finnish) · 8,191/1,179,478 alleles

Filtering AF 0.682% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.677%

Overall 0.555% 8,950/1,612,554 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	4.82%	21
European (non-Finnish)grpmax	0.694%	144
Finnishnot grpmax-eligible	0.41%	244
Remaining individualsnot grpmax-eligible	0.314%	319
Ashkenazi Jewishnot grpmax-eligible	0.25%	400
Admixed American	0.108%	923
African / African-American	0.092%	1,087
South Asian	0.056%	1,786
Middle Eastern	0.0165%	6,060

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser188=
Coding: c.564C>T
MANE Select: NM_017649
dbSNP: rs117691462
Type: single nucleotide variant
Location: chr10:102919044 (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-ser188 (accessed [today's date]).

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