Is CDON p.Pro1002Ser (c.3004C>T) pathogenic?

CDON p.Pro1002Ser (c.3004C>T) is classified Uncertain significance in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-23). AlphaMissense: ambiguous (0.3914); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CDON p.Pro1002Ser (c.3004C>T)?

CDON p.Pro1002Ser (c.3004C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDON p.Pro1002Ser (c.3004C>T) in the general population?

CDON p.Pro1002Ser (c.3004C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CDON p.Pro1002Ser (c.3004C>T)?

AlphaMissense predicts ambiguous (score 0.3914) — an in-silico prediction, not a clinical call.

CDON p.Pro1002Ser

c.3004C>T · VCV4839843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3914 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3914	ambiguous
REVEL	0.312	indeterminate
SaProt	LLR -5.72	tolerated
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	28.3	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 0.00167% Admixed American · 1/59,990 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,460,756 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,990
European (non-Finnish)	0.000254%	393,323

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: CDON
Protein: p.Pro1002Ser
Coding: c.3004C>T
MANE Select: NM_001378964
Type: single nucleotide variant
Location: chr11:125981321 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDON p.Pro1002Ala Uncertain significance ★ ⚠ same residue
CDON p.Ala1099Val Uncertain significance ★★ ⚠ same condition
CDON p.Ala495Val Uncertain significance ★★ ⚠ same condition
CDON p.Arg157Trp Uncertain significance ★★ ⚠ same condition
CDON p.Arg760Leu Uncertain significance ★★ ⚠ same condition
CDON p.Asn1222Asp Uncertain significance ★★ ⚠ same condition
CDON p.Gln1008Lys Uncertain significance ★★ ⚠ same condition
CDON p.Glu663Asp Uncertain significance ★★ ⚠ same condition

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/cdon-p-pro1002ser (accessed [today's date]).

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