Is DDOST p.Arg237= (c.711C>T) pathogenic?

DDOST p.Arg237= (c.711C>T) is classified Benign/Likely benign in DDOST (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-19). Low-frequency (popmax 2.53%, mid); Associated with DDOST-congenital disorder of glycosylation.

What condition is associated with DDOST p.Arg237= (c.711C>T)?

DDOST p.Arg237= (c.711C>T) is associated with DDOST-congenital disorder of glycosylation (ClinVar).

How common is DDOST p.Arg237= (c.711C>T) in the general population?

DDOST p.Arg237= (c.711C>T) is low-frequency (popmax 2.53%, mid) (gnomAD).

How is DDOST-CDG inherited?

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

DDOST p.Arg237=

c.711C>T · rs34189097 · VCV95262

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.53%, 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 -2.6	GERP -4.8
Overall
CADD	5.883	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.53% Middle Eastern · 151/5,976 alleles

Filtering AF 2.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.07%

Overall 0.12% 1,873/1,554,558 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.53%	40
Admixed American	0.313%	320
Remaining individualsnot grpmax-eligible	0.276%	363
Ashkenazi Jewishnot grpmax-eligible	0.244%	410
European (non-Finnish)	0.11%	912
African / African-American	0.0477%	2,095
South Asian	0.032%	3,121
Finnishnot grpmax-eligible	0.00499%	20,023
East Asian	0.00242%	41,248

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.Arg237=
Coding: c.711C>T
MANE Select: NM_005216
dbSNP: rs34189097
Type: single nucleotide variant
Location: chr1:20654306 (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.Arg237His Uncertain significance ★★ ⚠ same residue
DDOST p.Arg237Cys 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

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-arg237 (accessed [today's date]).

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