Is CDCP2 c.1117+15G>A pathogenic?

CDCP2 c.1117+15G>A is classified Uncertain significance in CDCP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.1734); Very rare (popmax 0.00119%, nfe).

How common is CDCP2 c.1117+15G>A in the general population?

CDCP2 c.1117+15G>A is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about CDCP2 c.1117+15G>A?

AlphaMissense predicts likely benign (score 0.1734) — an in-silico prediction, not a clinical call.

CDCP2 c.1117+15G>A

VCV4650986

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1734 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1734	likely benign
REVEL	0.127	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
Splice region	donor +15	near-intronic (+15 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.058	GERP 1.8
Non-coding constraint	Z 2.24	1 kb window · o/e 0.80 · regional · uncalibrated
Overall
CADD	4.42	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 0.00119% European (non-Finnish) · 14/1,180,036 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000958% 14/1,461,882 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
Coding: c.1117+15G>A
MANE Select: NM_001353655
Type: single nucleotide variant
Location: chr1:54139738 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.43

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+168C>G Uncertain significance ★ ⚠ same type
CDCP2 c.1117+184C>T Uncertain significance ★ ⚠ same type
CDCP2 c.1117+97C>T Uncertain significance ★ ⚠ same type
CDCP2 p.Ala138Thr 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-c-1117-plus-15g-a (accessed [today's date]).

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