Is CDON p.Phe1036Leu (c.3108C>A) pathogenic?

CDON p.Phe1036Leu (c.3108C>A) is classified Uncertain significance in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-29). AlphaMissense: likely pathogenic (0.8869); Very rare (popmax 0.0011%, nfe); Associated with congenital anomaly of kidney and urinary tract.

What condition is associated with CDON p.Phe1036Leu (c.3108C>A)?

CDON p.Phe1036Leu (c.3108C>A) is associated with congenital anomaly of kidney and urinary tract (ClinVar).

How common is CDON p.Phe1036Leu (c.3108C>A) in the general population?

CDON p.Phe1036Leu (c.3108C>A) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about CDON p.Phe1036Leu (c.3108C>A)?

AlphaMissense predicts likely pathogenic (score 0.8869) — an in-silico prediction, not a clinical call.

CDON p.Phe1036Leu

c.3108C>A · VCV4075078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8869 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital anomaly of kidney and urinary tract

Computational evidence

Protein change
AlphaMissense	0.8869	likely pathogenic · top 10% in CDON
REVEL	0.068	moderately benign-leaning
SaProt	LLR -4.84	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.077, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	14.62	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 0.0011% European (non-Finnish) · 13/1,180,032 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000889% 13/1,461,892 alleles · very rare

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.Phe1036Leu
Coding: c.3108C>A
MANE Select: NM_001378964
Type: single nucleotide variant
Location: chr11:125981217 (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

congenital anomaly of kidney and urinary tract — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
CDON p.Ala1099Val 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-phe1036leu (accessed [today's date]).

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