Is CDON p.Ser463= (c.1389A>C) pathogenic?

CDON p.Ser463= (c.1389A>C) is classified Likely benign in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-20). Ultra-rare (popmax 0.029%, eas); Associated with holoprosencephaly 11.

What condition is associated with CDON p.Ser463= (c.1389A>C)?

CDON p.Ser463= (c.1389A>C) is associated with holoprosencephaly 11 (ClinVar).

How common is CDON p.Ser463= (c.1389A>C) in the general population?

CDON p.Ser463= (c.1389A>C) is ultra-rare (popmax 0.029%, eas) (gnomAD).

CDON p.Ser463=

c.1389A>C · rs1434214033 · VCV1945328

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Conditions

holoprosencephaly 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.01	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -2.9
Overall
CADD	0.874	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.029% East Asian · 13/44,888 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.000805% 13/1,614,024 alleles · ultra-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.Ser463=
Coding: c.1389A>C
MANE Select: NM_001378964
dbSNP: rs1434214033
Type: single nucleotide variant
Location: chr11:126010504 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 463: a disulfide bond; the ig-like c2-type 5 domain

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

Disease context

holoprosencephaly 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDON p.Ser463Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
CDON p.Ser463Thr Uncertain significance ★ ⚠ same residue
CDON c.3276+1G>T Uncertain significance ★★ same condition
CDON c.640+1G>A Uncertain significance ★★ same condition
CDON c.*1805A>G Uncertain significance ★★ same condition
CDON c.*1816C>T Uncertain significance ★★ same condition
CDON c.*2349A>C Uncertain significance ★★ same condition
CDON c.*2377T>C 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-ser463 (accessed [today's date]).

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