Is CDON p.Asp1196= (c.3588C>T) pathogenic?

CDON p.Asp1196= (c.3588C>T) is classified Benign in CDON (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-17). Low-frequency (popmax 1.8%, afr); Associated with holoprosencephaly 11.

What condition is associated with CDON p.Asp1196= (c.3588C>T)?

CDON p.Asp1196= (c.3588C>T) is associated with holoprosencephaly 11 (ClinVar).

How common is CDON p.Asp1196= (c.3588C>T) in the general population?

CDON p.Asp1196= (c.3588C>T) is low-frequency (popmax 1.8%, afr) (gnomAD).

CDON p.Asp1196=

c.3588C>T · rs140895899 · VCV303491

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.8%, afr)

Conditions

holoprosencephaly 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.69 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.36	GERP -2.2
Overall
CADD	4.342	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.8% African / African-American · 1,352/75,022 alleles

Filtering AF 1.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.69%

Overall 0.0988% 1,594/1,614,040 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.8%	55
Admixed American	0.15%	667
Remaining individualsnot grpmax-eligible	0.13%	772
Middle Eastern	0.099%	1,010
South Asian	0.00879%	11,383
East Asian	0.00668%	14,961
European (non-Finnish)	0.00458%	21,851

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.Asp1196=
Coding: c.3588C>T
MANE Select: NM_001378964
dbSNP: rs140895899
Type: single nucleotide variant
Location: chr11:125961767 (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-asp1196 (accessed [today's date]).

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