Is CDON p.Ser1130Asn (c.3389G>A) pathogenic?

CDON p.Ser1130Asn (c.3389G>A) is classified Uncertain significance in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-14). AlphaMissense: ambiguous (0.3532); Absent from gnomAD v4.1; Associated with holoprosencephaly 11.

What condition is associated with CDON p.Ser1130Asn (c.3389G>A)?

CDON p.Ser1130Asn (c.3389G>A) is associated with holoprosencephaly 11 (ClinVar).

How common is CDON p.Ser1130Asn (c.3389G>A) in the general population?

CDON p.Ser1130Asn (c.3389G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDON p.Ser1130Asn (c.3389G>A)?

AlphaMissense predicts ambiguous (score 0.3532) — an in-silico prediction, not a clinical call.

CDON p.Ser1130Asn

c.3389G>A · rs1945658522 · VCV931554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3532 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

holoprosencephaly 11

Computational evidence

Protein change
AlphaMissense	0.3532	ambiguous
REVEL	0.032	moderately benign-leaning
SaProt	LLR -7.76	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 0.19	GERP -2.3, phastCons 0.84
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	13.06	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDON
Protein: p.Ser1130Asn
Coding: c.3389G>A
MANE Select: NM_001378964
dbSNP: rs1945658522
Type: single nucleotide variant
Location: chr11:125961966 (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

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

Similar variants

CDON p.Ser1130Arg 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-ser1130asn (accessed [today's date]).

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