Is CDON p.Ala495Val (c.1484C>T) pathogenic?

CDON p.Ala495Val (c.1484C>T) is classified Uncertain significance in CDON (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-04). AlphaMissense: ambiguous (0.343); Ultra-rare (popmax 0.0111%, eas); Associated with Inborn genetic diseases.

What condition is associated with CDON p.Ala495Val (c.1484C>T)?

CDON p.Ala495Val (c.1484C>T) is associated with Inborn genetic diseases, holoprosencephaly 11 (ClinVar).

How common is CDON p.Ala495Val (c.1484C>T) in the general population?

CDON p.Ala495Val (c.1484C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about CDON p.Ala495Val (c.1484C>T)?

AlphaMissense predicts ambiguous (score 0.343) — an in-silico prediction, not a clinical call.

CDON p.Ala495Val

c.1484C>T · rs749914707 · VCV2368618

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.343 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.343	ambiguous
REVEL	0.194	benign-leaning
SaProt	LLR -7.14	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	21.8	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 0.0111% East Asian · 5/44,874 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.0018% 29/1,613,920 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,975
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
Admixed American	0.00167%	59,994
European (non-Finnish)	0.00161%	62,104

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.Ala495Val
Coding: c.1484C>T
MANE Select: NM_001378964
dbSNP: rs749914707
Type: single nucleotide variant
Location: chr11:126010409 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 495: a disulfide bond; the ig-like c2-type 5 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

Also linked: holoprosencephaly 11

Similar variants

CDON p.Ala495= Likely benign ★ same residue
CDON c.3276+1G>T Uncertain significance ★★ same condition
CDON c.640+1G>A Uncertain significance ★★ same condition
CDON c.*1805A>G Uncertain significance ★★ same condition
CDON c.*1816C>T Uncertain significance ★★ same condition
CDON c.*2349A>C Uncertain significance ★★ same condition
CDON c.*2377T>C Uncertain significance ★★ same condition
CDON c.*2760A>G 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-ala495val (accessed [today's date]).

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