Is DDOST p.Asn191Lys (c.573C>A) pathogenic?

DDOST p.Asn191Lys (c.573C>A) is classified Uncertain significance in DDOST (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-25). AlphaMissense: likely pathogenic (0.9973); Ultra-rare (popmax 0.0109%, afr); Associated with DDOST-congenital disorder of glycosylation.

What condition is associated with DDOST p.Asn191Lys (c.573C>A)?

DDOST p.Asn191Lys (c.573C>A) is associated with DDOST-congenital disorder of glycosylation (ClinVar).

How common is DDOST p.Asn191Lys (c.573C>A) in the general population?

DDOST p.Asn191Lys (c.573C>A) is ultra-rare (popmax 0.0109%, afr) (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.Asn191Lys (c.573C>A)?

AlphaMissense predicts likely pathogenic (score 0.9973) — an in-silico prediction, not a clinical call.

DDOST p.Asn191Lys

c.573C>A · rs1038330038 · VCV1031522

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9973 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DDOST-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.9973	likely pathogenic · top 4% in DDOST
REVEL	0.6	indeterminate
SaProt	LLR -13.09	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -1.7
Regional constraint	o/e 0.92	unconstrained · MANE · 8,968 bp · p 0.046 · regional, not allelic
Overall
CADD	20.3	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 N208K vs ClinVar N191K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0109% African / African-American · 8/73,538 alleles

Filtering AF 0.00536% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00387%

Overall 0.000962% 15/1,559,860 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0109%	9,192
Admixed American	0.00954%	10,484
Remaining individualsnot grpmax-eligible	0.00165%	60,432
European (non-Finnish)	8.69e-05%	1,150,964

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.Asn191Lys
Coding: c.573C>A
MANE Select: NM_005216
dbSNP: rs1038330038
Type: single nucleotide variant
Location: chr1:20654686 (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.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-asn191lys (accessed [today's date]).

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