Is CDCP2 p.Cys336Tyr (c.1007G>A) pathogenic?

CDCP2 p.Cys336Tyr (c.1007G>A) is classified Uncertain significance in CDCP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-25). AlphaMissense: likely pathogenic (0.9901); Very rare (popmax 0.00223%, eas).

How common is CDCP2 p.Cys336Tyr (c.1007G>A) in the general population?

CDCP2 p.Cys336Tyr (c.1007G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CDCP2 p.Cys336Tyr (c.1007G>A)?

AlphaMissense predicts likely pathogenic (score 0.9901) — an in-silico prediction, not a clinical call.

CDCP2 p.Cys336Tyr

c.1007G>A · VCV3998745

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9901 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9901	likely pathogenic · top 5% in CDCP2
REVEL	0.821	moderately pathogenic-leaning
SaProt	LLR -11.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.30	donor gain · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.072 · regional, not allelic
Overall
CADD	28.9	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 0.00223% East Asian · 1/44,878 alleles

Overall 6.84e-05% 1/1,461,738 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: CDCP2
Protein: p.Cys336Tyr
Coding: c.1007G>A
MANE Select: NM_001353655
Type: single nucleotide variant
Location: chr1:54139863 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.43
Residue 336: a disulfide bond; the cub 3 domain

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

Similar variants

CDCP2 p.Cys336Arg Uncertain significance ★ ⚠ same residue
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

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-cys336tyr (accessed [today's date]).

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