Is CDCP2 p.Gly219Val (c.656G>T) pathogenic?

CDCP2 p.Gly219Val (c.656G>T) is classified Uncertain significance in CDCP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely pathogenic (0.9362); Rare (popmax 0.145%, amr).

How common is CDCP2 p.Gly219Val (c.656G>T) in the general population?

CDCP2 p.Gly219Val (c.656G>T) is rare (popmax 0.145%, amr) (gnomAD).

What do computational predictors say about CDCP2 p.Gly219Val (c.656G>T)?

AlphaMissense predicts likely pathogenic (score 0.9362) — an in-silico prediction, not a clinical call.

CDCP2 p.Gly219Val

c.656G>T · VCV3829956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9362 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.145%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9362	likely pathogenic
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -16.59	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 7.5	GERP 0.87, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.072 · regional, not allelic
Overall
CADD	28.1	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 0.145% Admixed American · 86/59,472 alleles

Filtering AF 0.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.00541% 87/1,608,684 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.145%	692
Remaining individualsnot grpmax-eligible	0.00161%	62,226

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.Gly219Val
Coding: c.656G>T
MANE Select: NM_001353655
Type: single nucleotide variant
Location: chr1:54141205 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.43
Residue 219: 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-gly219val (accessed [today's date]).

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