Is DDOST p.Ser243Phe (c.728C>T) pathogenic?

DDOST p.Ser243Phe (c.728C>T) is classified Uncertain significance in DDOST (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-14). AlphaMissense: likely pathogenic (0.9972); Absent from gnomAD v4.1; Associated with DDOST-congenital disorder of glycosylation.

What condition is associated with DDOST p.Ser243Phe (c.728C>T)?

DDOST p.Ser243Phe (c.728C>T) is associated with DDOST-congenital disorder of glycosylation (ClinVar).

How common is DDOST p.Ser243Phe (c.728C>T) in the general population?

DDOST p.Ser243Phe (c.728C>T) is absent from gnomAD v4.1 (gnomAD).

How is DDOST-CDG inherited?

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

What do computational predictors say about DDOST p.Ser243Phe (c.728C>T)?

AlphaMissense predicts likely pathogenic (score 0.9972) — an in-silico prediction, not a clinical call.

DDOST p.Ser243Phe

c.728C>T · rs2053339801 · VCV864597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9972 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,552,584)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DDOST-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.9972	likely pathogenic · top 4% in DDOST
REVEL	0.95	strongly pathogenic-leaning
SaProt	LLR -11.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 8,968 bp · p 0.046 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S260F vs ClinVar S243F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,552,584). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DDOST
Protein: p.Ser243Phe
Coding: c.728C>T
MANE Select: NM_005216
dbSNP: rs2053339801
Type: single nucleotide variant
Location: chr1:20654289 (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 243: 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-ser243phe (accessed [today's date]).

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