Is DDOST c.645+9T>C pathogenic?

DDOST c.645+9T>C is classified Likely benign in DDOST (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-23). Ultra-rare (popmax 0.0191%, nfe); Associated with DDOST-congenital disorder of glycosylation.

What condition is associated with DDOST c.645+9T>C?

DDOST c.645+9T>C is associated with DDOST-congenital disorder of glycosylation (ClinVar).

How common is DDOST c.645+9T>C in the general population?

DDOST c.645+9T>C is ultra-rare (popmax 0.0191%, nfe) (gnomAD).

How is DDOST-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DDOST c.645+9T>C

rs374229790 · VCV1158163

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0191%, nfe)

Conditions

DDOST-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.22	GERP -4.7
Non-coding constraint	Z 3.45	1 kb window · o/e 0.76 · regional · uncalibrated
Overall
CADD	2.752	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0191% European (non-Finnish) · 219/1,147,054 alleles

Filtering AF 0.017% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0162%

Overall 0.0147% 228/1,554,846 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0191%	5,238
African / African-American	0.00682%	14,670
Remaining individualsnot grpmax-eligible	0.00663%	15,076

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: DDOST
Coding: c.645+9T>C
MANE Select: NM_005216
dbSNP: rs374229790
Type: single nucleotide variant
Location: chr1:20654605 (GRCh38)
Gene constraint: LOEUF 0.747 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.27 · 6 PDB

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

Disease context

DDOST-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For DDOST-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DDOST p.Gln215His Pathogenic/Likely pathogenic ★★ ⚠ same condition
DDOST c.-18T>G Uncertain significance ★★ ⚠ same condition
DDOST p.Ala11Val Uncertain significance ★★ ⚠ same condition
DDOST p.Ala219Val Uncertain significance ★★ ⚠ same condition
DDOST p.Ala232Ser Uncertain significance ★★ ⚠ same condition
DDOST p.Ala415Thr Uncertain significance ★★ ⚠ same condition
DDOST p.Arg237His Uncertain significance ★★ ⚠ same condition
DDOST p.Arg280Cys 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/ddost-c-645-plus-9t-c (accessed [today's date]).

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