Is CDON p.Pro3= (c.9G>A) pathogenic?

CDON p.Pro3= (c.9G>A) is classified Benign in CDON (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-21). Low-frequency (popmax 3.09%, afr); Associated with holoprosencephaly 11.

What condition is associated with CDON p.Pro3= (c.9G>A)?

CDON p.Pro3= (c.9G>A) is associated with holoprosencephaly 11 (ClinVar).

How common is CDON p.Pro3= (c.9G>A) in the general population?

CDON p.Pro3= (c.9G>A) is low-frequency (popmax 3.09%, afr) (gnomAD).

CDON p.Pro3=

c.9G>A · rs113593771 · VCV260806

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.09%, afr)

Conditions

holoprosencephaly 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -4.8
Overall
CADD	3.623	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.09% African / African-American · 2,317/74,942 alleles

Filtering AF 2.99% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.94%

Overall 0.18% 2,893/1,611,286 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.09%	32
Remaining individualsnot grpmax-eligible	0.239%	419
Admixed American	0.233%	429
Middle Eastern	0.132%	756
European (non-Finnish)	0.0222%	4,511
South Asian	0.0154%	6,501
East Asian	0.00892%	11,216

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.Pro3=
Coding: c.9G>A
MANE Select: NM_001378964
dbSNP: rs113593771
Type: single nucleotide variant
Location: chr11:126023468 (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

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

Similar variants

CDON p.Pro3Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
CDON p.Pro3Leu 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-pro3 (accessed [today's date]).

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