Is DDOST p.Val96Met (c.286G>A) pathogenic?

DDOST p.Val96Met (c.286G>A) is classified Uncertain significance in DDOST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-15). AlphaMissense: ambiguous (0.354); Very rare (popmax 0.00333%, amr); Associated with DDOST-congenital disorder of glycosylation.

What condition is associated with DDOST p.Val96Met (c.286G>A)?

DDOST p.Val96Met (c.286G>A) is associated with DDOST-congenital disorder of glycosylation (ClinVar).

How common is DDOST p.Val96Met (c.286G>A) in the general population?

DDOST p.Val96Met (c.286G>A) is very rare (popmax 0.00333%, amr) (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.Val96Met (c.286G>A)?

AlphaMissense predicts ambiguous (score 0.354) — an in-silico prediction, not a clinical call.

DDOST p.Val96Met

c.286G>A · VCV4748424

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.354 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

DDOST-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.354	ambiguous
REVEL	0.608	indeterminate
SaProt	LLR -10.62	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 8,968 bp · p 0.046 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V113M vs ClinVar V96M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,006 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000372% 6/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,003
South Asian	0.0022%	45,543
African / African-American	0.00133%	74,932
European (non-Finnish)	8.47e-05%	1,179,976

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.Val96Met
Coding: c.286G>A
MANE Select: NM_005216
Type: single nucleotide variant
Location: chr1:20656167 (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 96: 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.Val96Ala 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-val96met (accessed [today's date]).

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