Is DOLK p.Ala435fs (c.1302_1311del) pathogenic?

DOLK p.Ala435fs (c.13021311del) is classified Uncertain significance in DOLK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). Absent from gnomAD; Associated with DK1-congenital disorder of glycosylation.

What condition is associated with DOLK p.Ala435fs (c.1302_1311del)?

DOLK p.Ala435fs (c.1302_1311del) is associated with DK1-congenital disorder of glycosylation (ClinVar).

How common is DOLK p.Ala435fs (c.1302_1311del) in the general population?

DOLK p.Ala435fs (c.1302_1311del) is absent from gnomAD (gnomAD).

How is DK1-CDG inherited?

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

DOLK p.Ala435fs

c.1302_1311del · rs1841656668 · VCV2069024

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

DK1-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP -1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: DOLK
Protein: p.Ala435fs
Coding: c.1302_1311del
MANE Select: NM_014908
dbSNP: rs1841656668
Type: Deletion
Location: chr9:128945993 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.37
Residue 435: a UniProt-annotated variant site (in cdg1m)

Full DOLK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DK1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For DK1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DOLK p.Ala435Pro Uncertain significance ★★ ⚠ same residue
DOLK p.Ala435Thr Uncertain significance ★ ⚠ same residue
DOLK p.Cys426fs Conflicting classifications of pathogenicity ★ same condition
DOLK p.Gln219fs Uncertain significance ★ same condition
DOLK p.Gln428fs Uncertain significance ★ same condition
DOLK p.Ile419fs Uncertain significance ★ same condition
DOLK p.Leu168_Phe174del Uncertain significance ★ same condition
DOLK p.Leu528del 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/dolk-p-ala435fs (accessed [today's date]).

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