Is CDCP1 p.Pro49Leu (c.146C>T) pathogenic?

CDCP1 p.Pro49Leu (c.146C>T) is classified Uncertain significance in CDCP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0853); Very rare (popmax 0.00167%, amr).

How common is CDCP1 p.Pro49Leu (c.146C>T) in the general population?

CDCP1 p.Pro49Leu (c.146C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CDCP1 p.Pro49Leu (c.146C>T)?

AlphaMissense predicts likely benign (score 0.0853) — an in-silico prediction, not a clinical call.

CDCP1 p.Pro49Leu

c.146C>T · VCV4223563

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0853 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0853	likely benign
REVEL	0.002	strongly benign-leaning
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.14	GERP -1.5
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.33 · regional, not allelic
Overall
CADD	4.827	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 0.00167% Admixed American · 1/60,006 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000558% 9/1,613,966 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,006
African / African-American	0.00134%	74,904
South Asian	0.0011%	91,068
European (non-Finnish)	0.000508%	196,671

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.Pro49Leu
Coding: c.146C>T
MANE Select: NM_022842
Type: single nucleotide variant
Location: chr3:45118558 (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.Pro49Arg 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-pro49leu (accessed [today's date]).

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