Is DDOST p.Thr199= (c.597G>A) pathogenic?

DDOST p.Thr199= (c.597G>A) is classified Uncertain significance in DDOST (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-15). Very rare (popmax 0.00564%, amr); Associated with DDOST-congenital disorder of glycosylation.

What condition is associated with DDOST p.Thr199= (c.597G>A)?

DDOST p.Thr199= (c.597G>A) is associated with DDOST-congenital disorder of glycosylation (ClinVar).

How common is DDOST p.Thr199= (c.597G>A) in the general population?

DDOST p.Thr199= (c.597G>A) is very rare (popmax 0.00564%, amr) (gnomAD).

How is DDOST-CDG inherited?

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

DDOST p.Thr199=

c.597G>A · rs755031163 · VCV1386079

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00564%, amr)

Conditions

DDOST-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.33	acceptor gain · deltas
Pangolin	Δ0.32	gain · loss 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -20	GERP -4.8
Overall
CADD	12.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00564% Admixed American · 3/53,192 alleles

Filtering AF 0.0015% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000815%

Overall 0.00134% 21/1,564,624 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00564%	17,731
Remaining individualsnot grpmax-eligible	0.0033%	30,314
European (non-Finnish)	0.00139%	72,090

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.Thr199=
Coding: c.597G>A
MANE Select: NM_005216
dbSNP: rs755031163
Type: single nucleotide variant
Location: chr1:20654662 (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.Thr199Met Uncertain significance ★★ ⚠ same residue
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

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-thr199 (accessed [today's date]).

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