Is CDON p.Phe1208fs (c.3622_3631del) pathogenic?

CDON p.Phe1208fs (c.36223631del) is classified Uncertain significance in CDON (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-17). Very rare (popmax 0.000763%, nfe); Associated with holoprosencephaly 11.

What condition is associated with CDON p.Phe1208fs (c.3622_3631del)?

CDON p.Phe1208fs (c.3622_3631del) is associated with holoprosencephaly 11 (ClinVar).

How common is CDON p.Phe1208fs (c.3622_3631del) in the general population?

CDON p.Phe1208fs (c.3622_3631del) is very rare (popmax 0.000763%, nfe) (gnomAD).

CDON p.Phe1208fs

c.3622_3631del · rs757327325 · VCV1433493

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Conditions

holoprosencephaly 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (19 of 20, 0 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 0.88, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,180,024 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000616% 9/1,461,842 alleles · very rare

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.Phe1208fs
Coding: c.3622_3631del
MANE Select: NM_001378964
dbSNP: rs757327325
Type: Deletion
Location: chr11:125961724 (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 p.Leu1106_Glu1107insTer Uncertain significance ★★ same condition
CDON p.Lys497_Tyr498insTer Uncertain significance ★★ same condition
CDON p.Lys999fs Uncertain significance ★★ same condition
CDON c.2363-5_2363-4del Uncertain significance ★ same condition
CDON p.Asn746fs Uncertain significance ★ same condition
CDON p.Asn856del Uncertain significance ★ same condition
CDON p.Gln319fs Uncertain significance ★ same condition
CDON c.2773+18_2773+20del Likely benign ★ 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-phe1208fs (accessed [today's date]).

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