Is CDON p.Pro29= (c.87T>G) pathogenic?

CDON p.Pro29= (c.87T>G) is classified Likely benign in CDON (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-29). Very rare (popmax 0.005%, amr); Associated with holoprosencephaly 11.

What condition is associated with CDON p.Pro29= (c.87T>G)?

CDON p.Pro29= (c.87T>G) is associated with holoprosencephaly 11 (ClinVar).

How common is CDON p.Pro29= (c.87T>G) in the general population?

CDON p.Pro29= (c.87T>G) is very rare (popmax 0.005%, amr) (gnomAD).

CDON p.Pro29=

c.87T>G · VCV3647920

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

holoprosencephaly 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.005	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -2.9, phastCons 1
Overall
CADD	9.434	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,016 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00328% 53/1,614,036 alleles · very rare exomes 46/1,461,678 · genomes 7/152,358 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,005
European (non-Finnish)	0.00398%	25,105
Remaining individualsnot grpmax-eligible	0.0032%	31,252
African / African-American	0.00133%	75,060

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.Pro29=
Coding: c.87T>G
MANE Select: NM_001378964
Type: single nucleotide variant
Location: chr11:126021510 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 29: the ig-like c2-type 1 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-pro29 (accessed [today's date]).

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