Is CDCP1 p.Arg145His (c.434G>A) pathogenic?

CDCP1 p.Arg145His (c.434G>A) is classified Uncertain significance in CDCP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-23). AlphaMissense: likely benign (0.0774); Ultra-rare (popmax 0.0472%, sas).

How common is CDCP1 p.Arg145His (c.434G>A) in the general population?

CDCP1 p.Arg145His (c.434G>A) is ultra-rare (popmax 0.0472%, sas) (gnomAD).

What do computational predictors say about CDCP1 p.Arg145His (c.434G>A)?

AlphaMissense predicts likely benign (score 0.0774) — an in-silico prediction, not a clinical call.

CDCP1 p.Arg145His

c.434G>A · rs370503753 · VCV2280341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0774 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0472%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0774	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -7.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP 0.092, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 27 kb · p 7.2e-12 · regional, not allelic
Overall
CADD	19.79	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 0.0472% South Asian · 43/91,084 alleles

Filtering AF 0.036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0321%

Overall 0.00458% 74/1,614,150 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0472%	2,118
African / African-American	0.00933%	10,719
Admixed American	0.00833%	12,005
Remaining individualsnot grpmax-eligible	0.008%	12,502
European (non-Finnish)	0.00119%	84,288

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.Arg145His
Coding: c.434G>A
MANE Select: NM_022842
dbSNP: rs370503753
Type: single nucleotide variant
Location: chr3:45112304 (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-arg145his (accessed [today's date]).

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