Is CDON p.Pro7Leu (c.20C>T) pathogenic?

CDON p.Pro7Leu (c.20C>T) is classified Likely benign in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). AlphaMissense: likely benign (0.2735); Very rare (popmax 0.0095%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDON p.Pro7Leu (c.20C>T)?

CDON p.Pro7Leu (c.20C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDON p.Pro7Leu (c.20C>T) in the general population?

CDON p.Pro7Leu (c.20C>T) is very rare (popmax 0.0095%, nfe) (gnomAD).

What do computational predictors say about CDON p.Pro7Leu (c.20C>T)?

AlphaMissense predicts likely benign (score 0.2735) — an in-silico prediction, not a clinical call.

CDON p.Pro7Leu

c.20C>T · VCV3489707

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0095%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2735	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -5.50	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 3.5	GERP 0.69, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	15.94	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 0.0095% European (non-Finnish) · 112/1,179,032 alleles

Filtering AF 0.00805% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00752%

Overall 0.00719% 116/1,612,998 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0095%	10,527
Remaining individualsnot grpmax-eligible	0.0032%	31,239
Admixed American	0.00167%	60,012
African / African-American	0.00133%	74,992

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.Pro7Leu
Coding: c.20C>T
MANE Select: NM_001378964
Type: single nucleotide variant
Location: chr11:126023457 (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.Pro7= Likely benign ★ 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-pro7leu (accessed [today's date]).

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