Is CDCP1 p.Val546Ile (c.1636G>A) pathogenic?

CDCP1 p.Val546Ile (c.1636G>A) is classified Likely benign in CDCP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely benign (0.0546); Ultra-rare (popmax 0.0331%, mid).

How common is CDCP1 p.Val546Ile (c.1636G>A) in the general population?

CDCP1 p.Val546Ile (c.1636G>A) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

What do computational predictors say about CDCP1 p.Val546Ile (c.1636G>A)?

AlphaMissense predicts likely benign (score 0.0546) — an in-silico prediction, not a clinical call.

CDCP1 p.Val546Ile

c.1636G>A · VCV3488595

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0546 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0546	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -5.89	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 -0.92	GERP -3.1
Regional constraint	o/e 0.78	unconstrained · MANE · 27 kb · p 7.2e-12 · regional, not allelic
Overall
CADD	0.307	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 0.0331% Middle Eastern · 2/6,034 alleles

Filtering AF 0.00584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.00419% 67/1,599,794 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,017
Admixed American	0.00676%	14,785
African / African-American	0.00668%	14,966
Remaining individualsnot grpmax-eligible	0.00644%	15,517
European (non-Finnish)	0.00426%	23,474
East Asian	0.00224%	44,672
South Asian	0.00111%	89,782

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.Val546Ile
Coding: c.1636G>A
MANE Select: NM_022842
Type: single nucleotide variant
Location: chr3:45091530 (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-val546ile (accessed [today's date]).

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