Is CDON p.Pro1002Ala (c.3004C>G) pathogenic?

CDON p.Pro1002Ala (c.3004C>G) is classified Uncertain significance in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-20). AlphaMissense: likely benign (0.2435); Very rare (popmax 0.0011%, sas).

How common is CDON p.Pro1002Ala (c.3004C>G) in the general population?

CDON p.Pro1002Ala (c.3004C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CDON p.Pro1002Ala (c.3004C>G)?

AlphaMissense predicts likely benign (score 0.2435) — an in-silico prediction, not a clinical call.

CDON p.Pro1002Ala

c.3004C>G · rs1169452825 · VCV1303531

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2435 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2435	likely benign
REVEL	0.442	indeterminate
SaProt	LLR -6.28	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.25 · evaluated, not missing
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	24.6	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 0.0011% South Asian · 1/91,060 alleles

Overall 6.85e-05% 1/1,460,756 alleles · very rare

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.Pro1002Ala
Coding: c.3004C>G
MANE Select: NM_001378964
dbSNP: rs1169452825
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

Similar variants

CDON p.Pro1002Ser Uncertain significance ★ ⚠ same residue
CDON c.3276+1G>T Uncertain significance ★★ same type
CDON c.640+1G>A Uncertain significance ★★ same type
CDON c.*1805A>G Uncertain significance ★★ same type
CDON c.*1816C>T Uncertain significance ★★ same type
CDON c.*2349A>C Uncertain significance ★★ same type
CDON c.*2377T>C Uncertain significance ★★ same type
CDON c.*2760A>G 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/cdon-p-pro1002ala (accessed [today's date]).

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