Is CNNM2 p.Ser32Ile (c.95G>T) pathogenic?

CNNM2 p.Ser32Ile (c.95G>T) is classified Likely benign in CNNM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-11). AlphaMissense: likely benign (0.167); Very rare (popmax 0.00283%, nfe).

How common is CNNM2 p.Ser32Ile (c.95G>T) in the general population?

CNNM2 p.Ser32Ile (c.95G>T) is very rare (popmax 0.00283%, nfe) (gnomAD).

What do computational predictors say about CNNM2 p.Ser32Ile (c.95G>T)?

AlphaMissense predicts likely benign (score 0.167) — an in-silico prediction, not a clinical call.

CNNM2 p.Ser32Ile

c.95G>T · rs749255923 · VCV2909399

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.167 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00283%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.167	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -8.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 150 bp · p 0.0044 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00283% European (non-Finnish) · 33/1,167,802 alleles

Filtering AF 0.00201% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00177%

Overall 0.00702% 111/1,581,042 alleles · very rare exomes 97/1,428,862 · genomes 14/152,180 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.127%	785
European (non-Finnish)grpmax	0.00283%	35,388
Admixed American	0.0018%	55,570
Remaining individualsnot grpmax-eligible	0.00164%	61,136

Finnish 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.Ser32Ile
Coding: c.95G>T
MANE Select: NM_017649
dbSNP: rs749255923
Type: single nucleotide variant
Location: chr10:102918575 (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

Similar variants

CNNM2 p.Ser32Asn Uncertain significance ★ ⚠ same residue
CNNM2 p.Ser32= Likely benign ★ same residue
CNNM2 p.Arg602Ter Likely pathogenic ★★ same type
CNNM2 p.Asn327Ser Likely pathogenic ★★ same type
CNNM2 p.Glu122Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
CNNM2 p.Glu357Lys Pathogenic ★★ same type
CNNM2 p.Ser269Trp Pathogenic/Likely pathogenic ★★ same type
CNNM2 c.1904-6C>G Uncertain significance ★★ same type

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-ser32ile (accessed [today's date]).

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