Is CDON p.Pro432= (c.1296G>A) pathogenic?

CDON p.Pro432= (c.1296G>A) is classified Benign in CDON (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-26). Common (popmax 5.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with holoprosencephaly 11.

What condition is associated with CDON p.Pro432= (c.1296G>A)?

CDON p.Pro432= (c.1296G>A) is associated with holoprosencephaly 11 (ClinVar).

CDON p.Pro432=

Q: How common is CDON p.Pro432= (c.1296G>A) in the general population?

CDON p.Pro432= (c.1296G>A) is common (popmax 5.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1296G>A · rs11220313 · VCV260782

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 5.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

holoprosencephaly 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.029	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -3.1
Overall
CADD	2.078	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.5% African / African-American · 4,123/75,008 alleles

Filtering AF 5.36% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.3%

Overall 0.293% 4,732/1,614,080 alleles · common exomes 2,341/1,461,834 · genomes 2,391/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.5%	18
Admixed American	0.453%	221
Remaining individualsnot grpmax-eligible	0.33%	303
Middle Eastern	0.198%	505
South Asian	0.0165%	6,071
European (non-Finnish)	0.00881%	11,346

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.Pro432=
Coding: c.1296G>A
MANE Select: NM_001378964
dbSNP: rs11220313
Type: single nucleotide variant
Location: chr11:126010597 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 432: 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 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
CDON c.*2760A>G Uncertain significance ★★ same condition
CDON p.Ala1099Val 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-pro432 (accessed [today's date]).

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