Is CDON p.Asp400= (c.1200C>T) pathogenic?

CDON p.Asp400= (c.1200C>T) is classified Likely benign in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-01). Ultra-rare (popmax 0.0107%, afr); Associated with holoprosencephaly 11.

What condition is associated with CDON p.Asp400= (c.1200C>T)?

CDON p.Asp400= (c.1200C>T) is associated with holoprosencephaly 11 (ClinVar).

How common is CDON p.Asp400= (c.1200C>T) in the general population?

CDON p.Asp400= (c.1200C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

CDON p.Asp400=

c.1200C>T · VCV3668144

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

holoprosencephaly 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.037	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.63 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.4	GERP -0.33, phastCons 0.097
Overall
CADD	10.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/74,982 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00223% 36/1,612,366 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,373
Admixed American	0.00333%	29,999
East Asian	0.00223%	44,856
European (non-Finnish)	0.00195%	51,243
Remaining individualsnot grpmax-eligible	0.0016%	62,448
South Asian	0.0011%	90,952

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.Asp400=
Coding: c.1200C>T
MANE Select: NM_001378964
Type: single nucleotide variant
Location: chr11:126010693 (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 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-asp400 (accessed [today's date]).

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