Is CDON p.Ile798Val (c.2392A>G) pathogenic?

CDON p.Ile798Val (c.2392A>G) is classified Benign/Likely benign in CDON (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-15). AlphaMissense: likely benign (0.1182); Low-frequency (popmax 1.53%, afr); Associated with holoprosencephaly 11.

What condition is associated with CDON p.Ile798Val (c.2392A>G)?

CDON p.Ile798Val (c.2392A>G) is associated with holoprosencephaly 11 (ClinVar).

How common is CDON p.Ile798Val (c.2392A>G) in the general population?

CDON p.Ile798Val (c.2392A>G) is low-frequency (popmax 1.53%, afr) (gnomAD).

What do computational predictors say about CDON p.Ile798Val (c.2392A>G)?

AlphaMissense predicts likely benign (score 0.1182) — an in-silico prediction, not a clinical call.

CDON p.Ile798Val

c.2392A>G · rs142919781 · VCV303499

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1182 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.53%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

holoprosencephaly 11

Computational evidence

Protein change
AlphaMissense	0.1182	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -5.37	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 0.97	GERP 0.9, phastCons 0.8
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	13.61	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 1.53% African / African-American · 1,150/75,052 alleles

Filtering AF 1.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.43%

Overall 0.0898% 1,449/1,614,126 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.53%	65
Middle Eastern	0.33%	303
Remaining individualsnot grpmax-eligible	0.136%	735
Admixed American	0.115%	870
Ashkenazi Jewishnot grpmax-eligible	0.0946%	1,057
European (non-Finnish)	0.0078%	12,826
South Asian	0.00549%	18,217

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.Ile798Val
Coding: c.2392A>G
MANE Select: NM_001378964
dbSNP: rs142919781
Type: single nucleotide variant
Location: chr11:125995023 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 798: the fibronectin type-iii 2 domain

Full CDON gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

holoprosencephaly 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDON p.Ile798Met Uncertain significance ★ ⚠ 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-ile798val (accessed [today's date]).

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