Is CDON p.Lys924Glu (c.2770A>G) pathogenic?

CDON p.Lys924Glu (c.2770A>G) is classified Conflicting classifications of pathogenicity in CDON (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-20). AlphaMissense: ambiguous (0.4837); Very rare (popmax 0.00967%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDON p.Lys924Glu (c.2770A>G)?

CDON p.Lys924Glu (c.2770A>G) is associated with Inborn genetic diseases, holoprosencephaly 11 (ClinVar).

How common is CDON p.Lys924Glu (c.2770A>G) in the general population?

CDON p.Lys924Glu (c.2770A>G) is very rare (popmax 0.00967%, nfe) (gnomAD).

What do computational predictors say about CDON p.Lys924Glu (c.2770A>G)?

AlphaMissense predicts ambiguous (score 0.4837) — an in-silico prediction, not a clinical call.

CDON p.Lys924Glu

c.2770A>G · rs747965171 · VCV1491551

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4837 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00967%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4837	ambiguous
REVEL	0.35	indeterminate
SaProt	LLR -8.72	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00967% European (non-Finnish) · 114/1,179,226 alleles

Filtering AF 0.00818% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00761%

Overall 0.00713% 115/1,612,868 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00967%	10,344
Remaining individualsnot grpmax-eligible	0.0016%	62,408

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.Lys924Glu
Coding: c.2770A>G
MANE Select: NM_001378964
dbSNP: rs747965171
Type: single nucleotide variant
Location: chr11:125989640 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 924: the fibronectin type-iii 3 domain

Full CDON gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: holoprosencephaly 11

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-lys924glu (accessed [today's date]).

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