Is CPXM2 p.Arg560Ser (c.1678C>A) pathogenic?

CPXM2 p.Arg560Ser (c.1678C>A) is classified Uncertain significance in CPXM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely pathogenic (0.8133); Very rare (popmax 0.000509%, nfe).

How common is CPXM2 p.Arg560Ser (c.1678C>A) in the general population?

CPXM2 p.Arg560Ser (c.1678C>A) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about CPXM2 p.Arg560Ser (c.1678C>A)?

AlphaMissense predicts likely pathogenic (score 0.8133) — an in-silico prediction, not a clinical call.

CPXM2 p.Arg560Ser

c.1678C>A · VCV4656344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8133 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8133	likely pathogenic
REVEL	0.303	indeterminate
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
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	25.0	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 0.000509% European (non-Finnish) · 6/1,179,824 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000411% 6/1,461,550 alleles · very rare

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.Arg560Ser
Coding: c.1678C>A
MANE Select: NM_198148
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.Arg560Cys 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-arg560ser (accessed [today's date]).

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