Is CPXM1 p.Ser185= (c.555G>A) pathogenic?

CPXM1 p.Ser185= (c.555G>A) is classified Likely benign in CPXM1 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 0.00439%, sas); Associated with EBV-positive nodal T- and NK-cell lymphoma.

What condition is associated with CPXM1 p.Ser185= (c.555G>A)?

CPXM1 p.Ser185= (c.555G>A) is associated with EBV-positive nodal T- and NK-cell lymphoma (ClinVar).

How common is CPXM1 p.Ser185= (c.555G>A) in the general population?

CPXM1 p.Ser185= (c.555G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

CPXM1 p.Ser185=

c.555G>A · rs1195354489 · VCV2681210

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

EBV-positive nodal T- and NK-cell lymphoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.43	donor gain · deltas
Constraint at this position
Conservation	phyloP -16	GERP -3.8
Overall
CADD	12.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,084 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00149% 24/1,613,852 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,771
African / African-American	0.00267%	37,459
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.00136%	73,751

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: CPXM1
Protein: p.Ser185=
Coding: c.555G>A
MANE Select: NM_019609
dbSNP: rs1195354489
Type: single nucleotide variant
Location: chr20:2798187 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.78
Residue 185: a disulfide bond; the f5/8 type c domain

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

Disease context

EBV-positive nodal T- and NK-cell lymphoma

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-ser185 (accessed [today's date]).

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