Is CPXM2 p.Arg560Cys (c.1678C>T) pathogenic?

CPXM2 p.Arg560Cys (c.1678C>T) is classified Uncertain significance in CPXM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: ambiguous (0.5347); Ultra-rare (popmax 0.0267%, eas).

How common is CPXM2 p.Arg560Cys (c.1678C>T) in the general population?

CPXM2 p.Arg560Cys (c.1678C>T) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

What do computational predictors say about CPXM2 p.Arg560Cys (c.1678C>T)?

AlphaMissense predicts ambiguous (score 0.5347) — an in-silico prediction, not a clinical call.

CPXM2 p.Arg560Cys

c.1678C>T · rs778892334 · VCV3076979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5347 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Computational evidence

Protein change
AlphaMissense	0.5347	ambiguous
REVEL	0.413	indeterminate
SaProt	LLR -13.14	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 2.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 145 kb · p 0.015 · regional, not allelic
Overall
CADD	33.0	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 0.0267% East Asian · 12/44,876 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00316% 51/1,613,692 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,740
Remaining individualsnot grpmax-eligible	0.0048%	20,824
European (non-Finnish)	0.0028%	35,752
Finnishnot grpmax-eligible	0.00156%	64,004
African / African-American	0.00133%	74,908
South Asian	0.0011%	91,044

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: CPXM2
Protein: p.Arg560Cys
Coding: c.1678C>T
MANE Select: NM_198148
dbSNP: rs778892334
Type: single nucleotide variant
Location: chr10:123761971 (GRCh38)
Gene constraint: LOEUF 0.974 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.58
Residue 560: the peptidase m14 domain

Full CPXM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPXM2 p.Arg560Ser Uncertain significance ★ ⚠ same residue
CPXM2 c.1918-10T>C Benign ★★ same type
CPXM2 p.Ala172= Benign ★★ same type
CPXM2 p.Lys577Arg Benign ★★ same type
CPXM2 p.Ala153Asp Uncertain significance ★ ⚠ same type
CPXM2 p.Ala183Val Uncertain significance ★ ⚠ same type
CPXM2 p.Ala376Val Uncertain significance ★ ⚠ same type
CPXM2 p.Ala402Val 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/cpxm2-p-arg560cys (accessed [today's date]).

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