Is CDON p.Val1183= (c.3549C>T) pathogenic?

CDON p.Val1183= (c.3549C>T) is classified Benign in CDON (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-02). Common (popmax 31.8%, sas) — too common for a highly-penetrant pathogenic allele; Associated with holoprosencephaly 11.

What condition is associated with CDON p.Val1183= (c.3549C>T)?

CDON p.Val1183= (c.3549C>T) is associated with holoprosencephaly 11 (ClinVar).

CDON p.Val1183=

Q: How common is CDON p.Val1183= (c.3549C>T) in the general population?

CDON p.Val1183= (c.3549C>T) is common (popmax 31.8%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3549C>T · rs2276061 · VCV260797

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 31.8%, sas) — too common for a highly-penetrant pathogenic allele

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 -0.51	GERP -0.58
Overall
CADD	0.337	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.8% South Asian · 28,951/91,056 alleles

Filtering AF 31.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 31.4%

Overall 30.2% 488,083/1,613,642 alleles · common exomes 449,354/1,461,542 · genomes 38,729/152,100 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	31.8%	3
European (non-Finnish)	31.5%	3
Finnishnot grpmax-eligible	31.3%	3
Amishnot grpmax-eligible	30.2%	3
Remaining individualsnot grpmax-eligible	29.8%	3
Ashkenazi Jewishnot grpmax-eligible	29.5%	3
East Asian	28%	4
Admixed American	27.2%	4
Middle Eastern	25.1%	4
African / African-American	12.2%	8

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.Val1183=
Coding: c.3549C>T
MANE Select: NM_001378964
dbSNP: rs2276061
Type: single nucleotide variant
Location: chr11:125961806 (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-val1183 (accessed [today's date]).

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