Is CNNM2 p.Ser784Tyr (c.2351C>A) pathogenic?

CNNM2 p.Ser784Tyr (c.2351C>A) is classified Uncertain significance in CNNM2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-27). AlphaMissense: likely benign (0.197); Absent from gnomAD v4.1.

How common is CNNM2 p.Ser784Tyr (c.2351C>A) in the general population?

CNNM2 p.Ser784Tyr (c.2351C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNNM2 p.Ser784Tyr (c.2351C>A)?

AlphaMissense predicts likely benign (score 0.197) — an in-silico prediction, not a clinical call.

CNNM2 p.Ser784Tyr

c.2351C>A · VCV3602820

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.197 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,591,240)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.197	likely benign
REVEL	0.241	benign-leaning
SaProt	LLR -11.21	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 8,525 bp · p 0.026 · regional, not allelic
Overall
CADD	26.1	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

No allele count reported in gnomAD v4.1 (AN 1,591,240). 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.Ser784Tyr
Coding: c.2351C>A
MANE Select: NM_017649
Type: single nucleotide variant
Location: chr10:103076203 (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.Ser784Cys Uncertain significance ★ ⚠ 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
CNNM2 p.Ala44Val 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-ser784tyr (accessed [today's date]).

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