Is CDON p.Arg744= (c.2232G>A) pathogenic?

CDON p.Arg744= (c.2232G>A) is classified Likely benign in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). Absent from gnomAD v4.1; Associated with holoprosencephaly 11.

What condition is associated with CDON p.Arg744= (c.2232G>A)?

CDON p.Arg744= (c.2232G>A) is associated with holoprosencephaly 11 (ClinVar).

How common is CDON p.Arg744= (c.2232G>A) in the general population?

CDON p.Arg744= (c.2232G>A) is absent from gnomAD v4.1 (gnomAD).

CDON p.Arg744=

c.2232G>A · VCV3687744

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.81	GERP 0.98, phastCons 1
Overall
CADD	9.907	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDON
Protein: p.Arg744=
Coding: c.2232G>A
MANE Select: NM_001378964
Type: single nucleotide variant
Location: chr11:125997337 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 744: the fibronectin type-iii 2 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.Arg744Trp Uncertain significance ★ ⚠ same residue
CDON p.Arg744Gln 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-arg744 (accessed [today's date]).

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