Is CDON c.349+3G>A pathogenic?

CDON c.349+3G>A is classified Likely benign in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-07). Rare (popmax 0.116%, eas); Associated with holoprosencephaly 11.

What condition is associated with CDON c.349+3G>A?

CDON c.349+3G>A is associated with holoprosencephaly 11 (ClinVar).

How common is CDON c.349+3G>A in the general population?

CDON c.349+3G>A is rare (popmax 0.116%, eas) (gnomAD).

CDON c.349+3G>A

rs776591632 · VCV800240

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.116%, eas)

Conditions

holoprosencephaly 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +3	donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP 0.52, phastCons 1
Non-coding constraint	Z 2.47	1 kb window · o/e 0.75 · regional · uncalibrated
Overall
CADD	14.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.116% East Asian · 52/44,862 alleles

Filtering AF 0.0907% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0818%

Overall 0.00341% 55/1,613,710 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.116%	863
Remaining individualsnot grpmax-eligible	0.0032%	31,244
African / African-American	0.00133%	75,022

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
Coding: c.349+3G>A
MANE Select: NM_001378964
dbSNP: rs776591632
Type: single nucleotide variant
Location: chr11:126021245 (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 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-c-349-plus-3g-a (accessed [today's date]).

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