Is CDCP2 p.Arg213His (c.638G>A) pathogenic?

CDCP2 p.Arg213His (c.638G>A) is classified Likely benign in CDCP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0787); Rare (popmax 0.402%, afr).

How common is CDCP2 p.Arg213His (c.638G>A) in the general population?

CDCP2 p.Arg213His (c.638G>A) is rare (popmax 0.402%, afr) (gnomAD).

What do computational predictors say about CDCP2 p.Arg213His (c.638G>A)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

CDCP2 p.Arg213His

c.638G>A · VCV4223567

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.402%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.72	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 -15	GERP -4
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.072 · regional, not allelic
Overall
CADD	0.048	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 0.402% African / African-American · 302/75,074 alleles

Filtering AF 0.365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.35%

Overall 0.0245% 396/1,613,180 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.402%	249
Middle Eastern	0.0495%	2,019
Admixed American	0.0284%	3,525
Remaining individualsnot grpmax-eligible	0.024%	4,164
European (non-Finnish)	0.00466%	21,444
East Asian	0.00223%	44,878
South Asian	0.0022%	45,480
Finnishnot grpmax-eligible	0.00156%	63,964

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.Arg213His
Coding: c.638G>A
MANE Select: NM_001353655
Type: single nucleotide variant
Location: chr1:54141223 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.43
Residue 213: 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-arg213his (accessed [today's date]).

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