Is CDON p.Leu241Val (c.721T>G) pathogenic?

CDON p.Leu241Val (c.721T>G) is classified Uncertain significance in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-04). AlphaMissense: ambiguous (0.4471); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CDON p.Leu241Val (c.721T>G)?

CDON p.Leu241Val (c.721T>G) is associated with Inborn genetic diseases (ClinVar).

How common is CDON p.Leu241Val (c.721T>G) in the general population?

CDON p.Leu241Val (c.721T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDON p.Leu241Val (c.721T>G)?

AlphaMissense predicts ambiguous (score 0.4471) — an in-silico prediction, not a clinical call.

CDON p.Leu241Val

c.721T>G · VCV3831020

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4471 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4471	ambiguous
REVEL	0.665	pathogenic-leaning
SaProt	LLR -11.27	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -0.98, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	20.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDON
Protein: p.Leu241Val
Coding: c.721T>G
MANE Select: NM_001378964
Type: single nucleotide variant
Location: chr11:126017295 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 241: the ig-like c2-type 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

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-leu241val (accessed [today's date]).

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