Is DDOST p.Arg298= (c.894G>C) pathogenic?

DDOST p.Arg298= (c.894G>C) is classified Likely benign in DDOST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). Ultra-rare (popmax 0.0486%, nfe); Associated with DDOST-congenital disorder of glycosylation.

What condition is associated with DDOST p.Arg298= (c.894G>C)?

DDOST p.Arg298= (c.894G>C) is associated with DDOST-congenital disorder of glycosylation (ClinVar).

How common is DDOST p.Arg298= (c.894G>C) in the general population?

DDOST p.Arg298= (c.894G>C) is ultra-rare (popmax 0.0486%, nfe) (gnomAD).

How is DDOST-CDG inherited?

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

DDOST p.Arg298=

c.894G>C · rs145327708 · VCV1579112

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0486%, 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
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.2	GERP -4.1, phastCons 0.001
Overall
CADD	8.169	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0486% European (non-Finnish) · 573/1,179,618 alleles

Filtering AF 0.0453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0439%

Overall 0.0362% 584/1,613,430 alleles · ultra-rare exomes 554/1,461,286 · genomes 30/152,144 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0486%	2,059
African / African-American	0.00801%	12,484
Remaining individualsnot grpmax-eligible	0.0064%	15,614
Finnishnot grpmax-eligible	0.00156%	64,008

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.Arg298=
Coding: c.894G>C
MANE Select: NM_005216
dbSNP: rs145327708
Type: single nucleotide variant
Location: chr1:20653675 (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 298: an α-helix

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.Arg298Gln Benign ★★ ⚠ 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-arg298 (accessed [today's date]).

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