Is CDON p.Arg811His (c.2432G>A) pathogenic?

CDON p.Arg811His (c.2432G>A) is classified Likely benign in CDON (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-07). AlphaMissense: likely benign (0.2666); Ultra-rare (popmax 0.0847%, eas); Associated with Inborn genetic diseases.

What condition is associated with CDON p.Arg811His (c.2432G>A)?

CDON p.Arg811His (c.2432G>A) is associated with Inborn genetic diseases, holoprosencephaly 11 (ClinVar).

How common is CDON p.Arg811His (c.2432G>A) in the general population?

CDON p.Arg811His (c.2432G>A) is ultra-rare (popmax 0.0847%, eas) (gnomAD).

What do computational predictors say about CDON p.Arg811His (c.2432G>A)?

AlphaMissense predicts likely benign (score 0.2666) — an in-silico prediction, not a clinical call.

CDON p.Arg811His

c.2432G>A · rs200008378 · VCV715194

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2666 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0847%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2666	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -5.07	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 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	27.3	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 0.0847% East Asian · 38/44,880 alleles

Filtering AF 0.0634% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.056%

Overall 0.0123% 199/1,614,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0847%	1,181
South Asian	0.0187%	5,357
Admixed American	0.0167%	6,002
Remaining individualsnot grpmax-eligible	0.0144%	6,945
European (non-Finnish)	0.0102%	9,833
African / African-American	0.00533%	18,753
Finnishnot grpmax-eligible	0.00156%	64,004

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.Arg811His
Coding: c.2432G>A
MANE Select: NM_001378964
dbSNP: rs200008378
Type: single nucleotide variant
Location: chr11:125994983 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 811: the fibronectin type-iii 2 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 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
CDON p.Ala1099Val 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-arg811his (accessed [today's date]).

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