Is CDCP1 p.Phe480Ser (c.1439T>C) pathogenic?

CDCP1 p.Phe480Ser (c.1439T>C) is classified Uncertain significance in CDCP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: ambiguous (0.3987); Very rare (popmax 8.48e-05%, nfe).

How common is CDCP1 p.Phe480Ser (c.1439T>C) in the general population?

CDCP1 p.Phe480Ser (c.1439T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CDCP1 p.Phe480Ser (c.1439T>C)?

AlphaMissense predicts ambiguous (score 0.3987) — an in-silico prediction, not a clinical call.

CDCP1 p.Phe480Ser

c.1439T>C · VCV4650979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3987 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3987	ambiguous
REVEL	0.099	moderately benign-leaning
SaProt	LLR -7.57	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP -0.54, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 27 kb · p 7.2e-12 · regional, not allelic
Overall
CADD	21.5	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 8.48e-05% European (non-Finnish) · 1/1,179,928 alleles

Overall 6.84e-05% 1/1,461,754 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: CDCP1
Protein: p.Phe480Ser
Coding: c.1439T>C
MANE Select: NM_022842
Type: single nucleotide variant
Location: chr3:45093465 (GRCh38)
Gene constraint: LOEUF 0.601 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 78.13
Residue 480: a disulfide bond; the cub domain

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

Similar variants

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
CDCP1 p.Ala528Ser 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-phe480ser (accessed [today's date]).

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