Is DDOST p.Val170Ile (c.508G>A) pathogenic?

DDOST p.Val170Ile (c.508G>A) is classified Uncertain significance in DDOST (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-02). AlphaMissense: likely benign (0.1173); Rare (popmax 0.113%, nfe); Associated with DDOST-congenital disorder of glycosylation.

What condition is associated with DDOST p.Val170Ile (c.508G>A)?

DDOST p.Val170Ile (c.508G>A) is associated with DDOST-congenital disorder of glycosylation (ClinVar).

How common is DDOST p.Val170Ile (c.508G>A) in the general population?

DDOST p.Val170Ile (c.508G>A) is rare (popmax 0.113%, nfe) (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.Val170Ile (c.508G>A)?

AlphaMissense predicts likely benign (score 0.1173) — an in-silico prediction, not a clinical call.

DDOST p.Val170Ile

c.508G>A · rs111334879 · VCV295146

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1173 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.113%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DDOST-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.1173	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 8,968 bp · p 0.046 · regional, not allelic
Overall
CADD	22.0	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 V187I vs ClinVar V170I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.113% European (non-Finnish) · 1,339/1,179,996 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.0909% 1,467/1,614,094 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.113%	881
Remaining individualsnot grpmax-eligible	0.0848%	1,179
Finnishnot grpmax-eligible	0.05%	2,000
Admixed American	0.0417%	2,400
African / African-American	0.0147%	6,821
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
South Asian	0.00439%	22,769

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.Val170Ile
Coding: c.508G>A
MANE Select: NM_005216
dbSNP: rs111334879
Type: single nucleotide variant
Location: chr1:20655483 (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 170: 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.Val170Ala 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-val170ile (accessed [today's date]).

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