Is CDON p.Ala489= (c.1467T>A) pathogenic?

CDON p.Ala489= (c.1467T>A) is classified Likely benign in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-01). Very rare (popmax 0.000169%, nfe).

How common is CDON p.Ala489= (c.1467T>A) in the general population?

CDON p.Ala489= (c.1467T>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

CDON p.Ala489=

c.1467T>A · rs1372680069 · VCV3250787

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.052	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP -3.1, phastCons 0.001
Overall
CADD	1.786	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,004 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,830 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.Ala489=
Coding: c.1467T>A
MANE Select: NM_001378964
dbSNP: rs1372680069
Type: single nucleotide variant
Location: chr11:126010426 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 489: a disulfide bond; the ig-like c2-type 5 domain

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

Similar variants

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
CDON p.Ala1099Val 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-ala489 (accessed [today's date]).

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