Is CDCP2 p.Pro180Ser (c.538C>T) pathogenic?

CDCP2 p.Pro180Ser (c.538C>T) is classified Uncertain significance in CDCP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.0855); Ultra-rare (popmax 0.0199%, nfe).

How common is CDCP2 p.Pro180Ser (c.538C>T) in the general population?

CDCP2 p.Pro180Ser (c.538C>T) is ultra-rare (popmax 0.0199%, nfe) (gnomAD).

What do computational predictors say about CDCP2 p.Pro180Ser (c.538C>T)?

AlphaMissense predicts likely benign (score 0.0855) — an in-silico prediction, not a clinical call.

CDCP2 p.Pro180Ser

c.538C>T · rs150513591 · VCV3141062

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0855 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0199%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0855	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -3.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -4.2, phastCons 0.71
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.072 · regional, not allelic
Overall
CADD	8.323	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0199% European (non-Finnish) · 235/1,180,040 alleles

Filtering AF 0.0178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.017%

Overall 0.0147% 238/1,614,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0199%	5,021
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00133%	74,950

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: CDCP2
Protein: p.Pro180Ser
Coding: c.538C>T
MANE Select: NM_001353655
dbSNP: rs150513591
Type: single nucleotide variant
Location: chr1:54141323 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.43
Residue 180: the cub 2 domain

Full CDCP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDCP2 c.1117+105C>T Uncertain significance ★ ⚠ same type
CDCP2 c.1117+106C>T Uncertain significance ★ ⚠ same type
CDCP2 c.1117+10G>A Uncertain significance ★ ⚠ same type
CDCP2 c.1117+110G>T Uncertain significance ★ ⚠ same type
CDCP2 c.1117+15G>A Uncertain significance ★ ⚠ same type
CDCP2 c.1117+168C>G Uncertain significance ★ ⚠ same type
CDCP2 c.1117+184C>T Uncertain significance ★ ⚠ same type
CDCP2 c.1117+97C>T 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/cdcp2-p-pro180ser (accessed [today's date]).

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