Is CDON p.Ile693Met (c.2079C>G) pathogenic?

CDON p.Ile693Met (c.2079C>G) is classified Uncertain significance in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-18). AlphaMissense: likely benign (0.2162); Ultra-rare (popmax 0.0329%, mid); Associated with Inborn genetic diseases.

What condition is associated with CDON p.Ile693Met (c.2079C>G)?

CDON p.Ile693Met (c.2079C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CDON p.Ile693Met (c.2079C>G) in the general population?

CDON p.Ile693Met (c.2079C>G) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about CDON p.Ile693Met (c.2079C>G)?

AlphaMissense predicts likely benign (score 0.2162) — an in-silico prediction, not a clinical call.

CDON p.Ile693Met

c.2079C>G · VCV4224818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2162 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2162	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -7.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.63	GERP -1.5, phastCons 0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	15.62	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.000372% 6/1,611,424 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,041
Remaining individualsnot grpmax-eligible	0.0016%	62,418
European (non-Finnish)	0.000255%	392,536

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.Ile693Met
Coding: c.2079C>G
MANE Select: NM_001378964
Type: single nucleotide variant
Location: chr11:126001798 (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

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

Similar variants

CDON p.Ala1099Val Uncertain significance ★★ ⚠ same condition
CDON p.Ala495Val Uncertain significance ★★ ⚠ same condition
CDON p.Arg157Trp Uncertain significance ★★ ⚠ same condition
CDON p.Arg760Leu Uncertain significance ★★ ⚠ same condition
CDON p.Asn1222Asp Uncertain significance ★★ ⚠ same condition
CDON p.Gln1008Lys Uncertain significance ★★ ⚠ same condition
CDON p.Glu663Asp Uncertain significance ★★ ⚠ same condition
CDON p.Gly259Arg 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-ile693met (accessed [today's date]).

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