Is CNNM2 p.Tyr561= (c.1683T>C) pathogenic?

CNNM2 p.Tyr561= (c.1683T>C) is classified Likely benign in CNNM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-06). Absent from gnomAD v4.1.

How common is CNNM2 p.Tyr561= (c.1683T>C) in the general population?

CNNM2 p.Tyr561= (c.1683T>C) is absent from gnomAD v4.1 (gnomAD).

CNNM2 p.Tyr561=

c.1683T>C · VCV3661500

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.12	GERP -4.1, phastCons 0.78
Overall
CADD	5.743	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CNNM2
Protein: p.Tyr561=
Coding: c.1683T>C
MANE Select: NM_017649
Type: single nucleotide variant
Location: chr10:103049768 (GRCh38)
Gene constraint: LOEUF 0.312 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.70 · 7 PDB
Residue 561: the cbs 2 domain; a β-strand

Full CNNM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NT5C2 p.Glu561_Ter562insGlu Uncertain significance ★ same residue
NT5C2 p.Glu561_Ter562insGluGlu Uncertain significance ★ same residue
NT5C2 p.Glu561del Conflicting classifications of pathogenicity ★ 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

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-tyr561 (accessed [today's date]).

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