Is CDCP1 p.Gly752Ser (c.2254G>A) pathogenic?

CDCP1 p.Gly752Ser (c.2254G>A) is classified Uncertain significance in CDCP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-16). AlphaMissense: likely benign (0.0764); Ultra-rare (popmax 0.0154%, nfe).

How common is CDCP1 p.Gly752Ser (c.2254G>A) in the general population?

CDCP1 p.Gly752Ser (c.2254G>A) is ultra-rare (popmax 0.0154%, nfe) (gnomAD).

What do computational predictors say about CDCP1 p.Gly752Ser (c.2254G>A)?

AlphaMissense predicts likely benign (score 0.0764) — an in-silico prediction, not a clinical call.

CDCP1 p.Gly752Ser

c.2254G>A · rs201971199 · VCV2375631

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0764 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0764	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -5.14	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 1.7	GERP 1.9, phastCons 0.98
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

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 0.0154% European (non-Finnish) · 182/1,180,028 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.0118% 190/1,614,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0154%	6,484
Remaining individualsnot grpmax-eligible	0.0096%	10,414
Admixed American	0.00167%	59,998
African / African-American	0.00134%	74,904

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.Gly752Ser
Coding: c.2254G>A
MANE Select: NM_022842
dbSNP: rs201971199
Type: single nucleotide variant
Location: chr3:45085895 (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.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-gly752ser (accessed [today's date]).

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