Is CDCP2 p.Trp173Arg (c.517T>C) pathogenic?

CDCP2 p.Trp173Arg (c.517T>C) is classified Uncertain significance in CDCP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely pathogenic (0.99); Very rare (popmax 0.00331%, nfe).

How common is CDCP2 p.Trp173Arg (c.517T>C) in the general population?

CDCP2 p.Trp173Arg (c.517T>C) is very rare (popmax 0.00331%, nfe) (gnomAD).

What do computational predictors say about CDCP2 p.Trp173Arg (c.517T>C)?

AlphaMissense predicts likely pathogenic (score 0.99) — an in-silico prediction, not a clinical call.

CDCP2 p.Trp173Arg

c.517T>C · VCV4223572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.99 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00331%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.99	likely pathogenic · top 6% in CDCP2
REVEL	0.757	pathogenic-leaning
SaProt	LLR -14.50	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.072 · regional, not allelic
Overall
CADD	28.6	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 0.00331% European (non-Finnish) · 39/1,179,996 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.0026% 42/1,614,020 alleles · very rare exomes 37/1,461,794 · genomes 5/152,226 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00331%	30,256
African / African-American	0.00267%	37,476
Admixed American	0.00167%	60,004

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.Trp173Arg
Coding: c.517T>C
MANE Select: NM_001353655
Type: single nucleotide variant
Location: chr1:54141344 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.43
Residue 173: the cub 2 domain

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

Similar variants

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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
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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-trp173arg (accessed [today's date]).

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