Is CDON p.Arg357= (c.1069C>A) pathogenic?

CDON p.Arg357= (c.1069C>A) is classified Conflicting classifications of pathogenicity in CDON (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-03-10). Rare (popmax 0.147%, eas); Associated with holoprosencephaly 11.

What condition is associated with CDON p.Arg357= (c.1069C>A)?

CDON p.Arg357= (c.1069C>A) is associated with holoprosencephaly 11 (ClinVar).

How common is CDON p.Arg357= (c.1069C>A) in the general population?

CDON p.Arg357= (c.1069C>A) is rare (popmax 0.147%, eas) (gnomAD).

CDON p.Arg357=

c.1069C>A · rs200614048 · VCV702448

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.147%, eas)

Conditions

holoprosencephaly 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.188	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2, phastCons 1
Overall
CADD	5.986	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.147% East Asian · 66/44,868 alleles

Filtering AF 0.119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.00452% 73/1,614,074 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.147%	680
Remaining individualsnot grpmax-eligible	0.0096%	10,417
European (non-Finnish)	8.47e-05%	1,180,008

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.Arg357=
Coding: c.1069C>A
MANE Select: NM_001378964
dbSNP: rs200614048
Type: single nucleotide variant
Location: chr11:126015370 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 357: a disulfide bond; the ig-like c2-type 4 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-arg357 (accessed [today's date]).

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