Is CDCP1 p.Arg594Trp (c.1780C>T) pathogenic?

CDCP1 p.Arg594Trp (c.1780C>T) is classified Uncertain significance in CDCP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-04). AlphaMissense: likely benign (0.1535); Very rare (popmax 0.00769%, sas).

How common is CDCP1 p.Arg594Trp (c.1780C>T) in the general population?

CDCP1 p.Arg594Trp (c.1780C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about CDCP1 p.Arg594Trp (c.1780C>T)?

AlphaMissense predicts likely benign (score 0.1535) — an in-silico prediction, not a clinical call.

CDCP1 p.Arg594Trp

c.1780C>T · VCV3998727

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1535 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1535	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -11.26	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 0.96, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 27 kb · p 7.2e-12 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,060 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00155% 25/1,613,936 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,009
Admixed American	0.005%	20,000
Finnishnot grpmax-eligible	0.00313%	32,000
African / African-American	0.00267%	37,460
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000847%	117,999

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: CDCP1
Protein: p.Arg594Trp
Coding: c.1780C>T
MANE Select: NM_022842
Type: single nucleotide variant
Location: chr3:45091386 (GRCh38)
Gene constraint: LOEUF 0.601 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 78.13

Full CDCP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDCP1 p.Arg594Gln Uncertain significance ★ ⚠ same residue
CDCP1 p.Ala306= Benign ★★ same type
CDCP1 p.Arg763Gln Benign ★★ same type
CDCP1 p.Gly596Ser Benign ★★ same type
CDCP1 p.Ala212Val Uncertain significance ★ ⚠ same type
CDCP1 p.Ala320Thr Uncertain significance ★ ⚠ same type
CDCP1 p.Ala464Gly Uncertain significance ★ ⚠ same type
CDCP1 p.Ala521Gly 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/cdcp1-p-arg594trp (accessed [today's date]).

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