Is CPXM1 p.Pro256Ser (c.766C>T) pathogenic?

CPXM1 p.Pro256Ser (c.766C>T) is classified Uncertain significance in CPXM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely pathogenic (0.9042); Absent from gnomAD v4.1.

How common is CPXM1 p.Pro256Ser (c.766C>T) in the general population?

CPXM1 p.Pro256Ser (c.766C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPXM1 p.Pro256Ser (c.766C>T)?

AlphaMissense predicts likely pathogenic (score 0.9042) — an in-silico prediction, not a clinical call.

CPXM1 p.Pro256Ser

c.766C>T · rs868316533 · VCV3076972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9042 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,571,178)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9042	likely pathogenic
REVEL	0.971	strongly pathogenic-leaning
SaProt	LLR -9.10	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 6,295 bp · p 0.0064 · regional, not allelic
Overall
CADD	28.0	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

No allele count reported in gnomAD v4.1 (AN 1,571,178). 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: CPXM1
Protein: p.Pro256Ser
Coding: c.766C>T
MANE Select: NM_019609
dbSNP: rs868316533
Type: single nucleotide variant
Location: chr20:2797258 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.78
Residue 256: a disulfide bond; the f5/8 type c domain

Full CPXM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPXM1 p.Arg725His Uncertain significance ★★ ⚠ same type
CPXM1 p.Leu711= Benign ★★ same type
CPXM1 p.Ala108Thr Uncertain significance ★ ⚠ same type
CPXM1 p.Ala132Thr Uncertain significance ★ ⚠ same type
CPXM1 p.Ala21Pro Uncertain significance ★ ⚠ same type
CPXM1 p.Ala227Thr Uncertain significance ★ ⚠ same type
CPXM1 p.Ala269Pro Uncertain significance ★ ⚠ same type
CPXM1 p.Ala273Thr 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/cpxm1-p-pro256ser (accessed [today's date]).

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