Is CNNM2 p.Ala18Val (c.53C>T) pathogenic?

CNNM2 p.Ala18Val (c.53C>T) is classified Uncertain significance in CNNM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.1359); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CNNM2 p.Ala18Val (c.53C>T)?

CNNM2 p.Ala18Val (c.53C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CNNM2 p.Ala18Val (c.53C>T) in the general population?

CNNM2 p.Ala18Val (c.53C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNNM2 p.Ala18Val (c.53C>T)?

AlphaMissense predicts likely benign (score 0.1359) — an in-silico prediction, not a clinical call.

CNNM2 p.Ala18Val

c.53C>T · VCV4004319

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1359 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,602,334)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1359	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -7.47	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 3.1	GERP 0.79, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 150 bp · p 0.0044 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,602,334). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CNNM2
Protein: p.Ala18Val
Coding: c.53C>T
MANE Select: NM_017649
Type: single nucleotide variant
Location: chr10:102918533 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNNM2 p.Ala45Ser Uncertain significance ★★ ⚠ same condition
CNNM2 p.Arg153His Uncertain significance ★★ ⚠ same condition
CNNM2 p.Arg30Cys Uncertain significance ★★ ⚠ same condition
CNNM2 p.Arg679Cys Uncertain significance ★★ ⚠ same condition
CNNM2 p.Arg679His Uncertain significance ★★ ⚠ same condition
CNNM2 p.Asn657Ser Uncertain significance ★★ ⚠ same condition
CNNM2 p.Asn680Ser Uncertain significance ★★ ⚠ same condition
CNNM2 p.Gln826Pro 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-ala18val (accessed [today's date]).

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