Is DDOST p.Leu244= (c.732C>A) pathogenic?

DDOST p.Leu244= (c.732C>A) is classified Likely benign in DDOST (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-10). Rare (popmax 0.337%, mid); Associated with DDOST-congenital disorder of glycosylation.

What condition is associated with DDOST p.Leu244= (c.732C>A)?

DDOST p.Leu244= (c.732C>A) is associated with DDOST-congenital disorder of glycosylation (ClinVar).

How common is DDOST p.Leu244= (c.732C>A) in the general population?

DDOST p.Leu244= (c.732C>A) is rare (popmax 0.337%, mid) (gnomAD).

How is DDOST-CDG inherited?

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

DDOST p.Leu244=

c.732C>A · rs149114970 · VCV387059

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.337%, mid)

Conditions

DDOST-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.4	GERP -4.8
Overall
CADD	1.037	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.337% Middle Eastern · 20/5,936 alleles

Filtering AF 0.223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.187%

Overall 0.0154% 239/1,552,344 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.337%	297
South Asian	0.113%	885
Admixed American	0.0274%	3,649
Remaining individualsnot grpmax-eligible	0.0249%	4,008
European (non-Finnish)	0.00776%	12,891
African / African-American	0.00546%	18,308
Finnishnot grpmax-eligible	0.00334%	29,978

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
Protein: p.Leu244=
Coding: c.732C>A
MANE Select: NM_005216
dbSNP: rs149114970
Type: single nucleotide variant
Location: chr1:20654285 (GRCh38)
Gene constraint: LOEUF 0.747 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.27 · 6 PDB
Residue 244: a β-strand

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-p-leu244 (accessed [today's date]).

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