Is CPXM2 p.Arg304Cys (c.910C>T) pathogenic?

CPXM2 p.Arg304Cys (c.910C>T) is classified Uncertain significance in CPXM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.7369); Very rare (popmax 0.00268%, afr).

How common is CPXM2 p.Arg304Cys (c.910C>T) in the general population?

CPXM2 p.Arg304Cys (c.910C>T) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about CPXM2 p.Arg304Cys (c.910C>T)?

AlphaMissense predicts likely pathogenic (score 0.7369) — an in-silico prediction, not a clinical call.

CPXM2 p.Arg304Cys

c.910C>T · VCV4656346

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7369 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7369	likely pathogenic
REVEL	0.737	pathogenic-leaning
SaProt	LLR -10.62	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP -0.41, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 145 kb · p 0.015 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00268% African / African-American · 2/74,740 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.0018% 29/1,607,282 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,370
European (non-Finnish)	0.00204%	48,916
Admixed American	0.00167%	59,982
Remaining individualsnot grpmax-eligible	0.00161%	62,266
South Asian	0.0011%	90,948

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.Arg304Cys
Coding: c.910C>T
MANE Select: NM_198148
Type: single nucleotide variant
Location: chr10:123780235 (GRCh38)
Gene constraint: LOEUF 0.974 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.58

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

Similar variants

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
CPXM2 p.Ala524Ser 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-arg304cys (accessed [today's date]).

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