Is DDOST p.Ala260Val (c.779C>T) pathogenic?

DDOST p.Ala260Val (c.779C>T) is classified Uncertain significance in DDOST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.0709); Very rare (popmax 0.00714%, sas); Associated with DDOST-congenital disorder of glycosylation.

What condition is associated with DDOST p.Ala260Val (c.779C>T)?

DDOST p.Ala260Val (c.779C>T) is associated with DDOST-congenital disorder of glycosylation (ClinVar).

How common is DDOST p.Ala260Val (c.779C>T) in the general population?

DDOST p.Ala260Val (c.779C>T) is very rare (popmax 0.00714%, sas) (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.Ala260Val (c.779C>T)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

DDOST p.Ala260Val

c.779C>T · VCV4812198

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00714%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DDOST-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -4.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -0.84, phastCons 0.01
Regional constraint	o/e 0.92	unconstrained · MANE · 8,968 bp · p 0.046 · regional, not allelic
Overall
CADD	14.07	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 A277V vs ClinVar A260V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00714% South Asian · 6/84,026 alleles

Filtering AF 0.00306% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00208%

Overall 0.00252% 39/1,550,568 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00714%	14,004
Remaining individualsnot grpmax-eligible	0.005%	19,997
East Asian	0.00488%	20,474
African / African-American	0.00274%	36,501
European (non-Finnish)	0.00218%	45,879
Admixed American	0.00196%	50,984

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.Ala260Val
Coding: c.779C>T
MANE Select: NM_005216
Type: single nucleotide variant
Location: chr1:20654238 (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.Ala260= Likely 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-ala260val (accessed [today's date]).

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