Is CDON p.Leu68= (c.202T>C) pathogenic?

CDON p.Leu68= (c.202T>C) is classified Likely benign in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). Ultra-rare (popmax 0.0706%, afr); Associated with Inborn genetic diseases.

What condition is associated with CDON p.Leu68= (c.202T>C)?

CDON p.Leu68= (c.202T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CDON p.Leu68= (c.202T>C) in the general population?

CDON p.Leu68= (c.202T>C) is ultra-rare (popmax 0.0706%, afr) (gnomAD).

CDON p.Leu68=

c.202T>C · rs373096471 · VCV3141681

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0706%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.011	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.5	GERP -4.8
Overall
CADD	0.811	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0706% African / African-American · 53/75,040 alleles

Filtering AF 0.0554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.05%

Overall 0.00415% 67/1,614,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0706%	1,416
Admixed American	0.005%	20,009
East Asian	0.00446%	22,430
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)	0.000593%	168,572

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.Leu68=
Coding: c.202T>C
MANE Select: NM_001378964
dbSNP: rs373096471
Type: single nucleotide variant
Location: chr11:126021395 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 68: a disulfide bond; the ig-like c2-type 1 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

Similar variants

CDON p.Leu68Met Uncertain significance ★ ⚠ same residue
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

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-leu68 (accessed [today's date]).

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