Is CDON p.Ile386Met (c.1158T>G) pathogenic?

CDON p.Ile386Met (c.1158T>G) is classified Uncertain significance in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-04). AlphaMissense: likely benign (0.2566); Very rare (popmax 0.00167%, amr).

How common is CDON p.Ile386Met (c.1158T>G) in the general population?

CDON p.Ile386Met (c.1158T>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CDON p.Ile386Met (c.1158T>G)?

AlphaMissense predicts likely benign (score 0.2566) — an in-silico prediction, not a clinical call.

CDON p.Ile386Met

c.1158T>G · VCV3907405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2566 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2566	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -7.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.6	GERP -0.64, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	20.6	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 0.00167% Admixed American · 1/60,006 alleles

Overall 0.000124% 2/1,614,040 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,006
African / African-American	0.00133%	74,940

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.Ile386Met
Coding: c.1158T>G
MANE Select: NM_001378964
Type: single nucleotide variant
Location: chr11:126015281 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 386: the ig-like c2-type 4 domain

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

Similar variants

CDON p.Ile386Thr Uncertain significance ★ ⚠ same residue
CDON c.3276+1G>T Uncertain significance ★★ same type
CDON c.640+1G>A Uncertain significance ★★ same type
CDON c.*1805A>G Uncertain significance ★★ same type
CDON c.*1816C>T Uncertain significance ★★ same type
CDON c.*2349A>C Uncertain significance ★★ same type
CDON c.*2377T>C Uncertain significance ★★ same type
CDON c.*2760A>G Uncertain significance ★★ same type

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-ile386met (accessed [today's date]).

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