Is CDCP2 p.Val148Ile (c.442G>A) pathogenic?

CDCP2 p.Val148Ile (c.442G>A) is classified Uncertain significance in CDCP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.0767); Ultra-rare (popmax 0.0344%, sas).

How common is CDCP2 p.Val148Ile (c.442G>A) in the general population?

CDCP2 p.Val148Ile (c.442G>A) is ultra-rare (popmax 0.0344%, sas) (gnomAD).

What do computational predictors say about CDCP2 p.Val148Ile (c.442G>A)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

CDCP2 p.Val148Ile

c.442G>A · rs372468657 · VCV3141059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0344%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -7.50	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 0.82, phastCons 0.9
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.072 · regional, not allelic
Overall
CADD	17.51	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 0.0344% South Asian · 31/90,008 alleles

Filtering AF 0.0249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0216%

Overall 0.00704% 113/1,605,164 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0344%	2,903
Admixed American	0.0119%	8,397
African / African-American	0.00669%	14,940
Remaining individualsnot grpmax-eligible	0.00644%	15,523
European (non-Finnish)	0.00553%	18,079
East Asian	0.00223%	44,784

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: CDCP2
Protein: p.Val148Ile
Coding: c.442G>A
MANE Select: NM_001353655
dbSNP: rs372468657
Type: single nucleotide variant
Location: chr1:54141419 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.43
Residue 148: a disulfide bond; the cub 2 domain

Full CDCP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDCP2 c.1117+105C>T Uncertain significance ★ ⚠ same type
CDCP2 c.1117+106C>T Uncertain significance ★ ⚠ same type
CDCP2 c.1117+10G>A Uncertain significance ★ ⚠ same type
CDCP2 c.1117+110G>T Uncertain significance ★ ⚠ same type
CDCP2 c.1117+15G>A Uncertain significance ★ ⚠ same type
CDCP2 c.1117+168C>G Uncertain significance ★ ⚠ same type
CDCP2 c.1117+184C>T Uncertain significance ★ ⚠ same type
CDCP2 c.1117+97C>T 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/cdcp2-p-val148ile (accessed [today's date]).

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