Is DOLK p.Met1fs (c.1dup) pathogenic?

DOLK p.Met1fs (c.1dup) is classified Benign/Likely benign in DOLK (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-03). Rare (popmax 0.881%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DOLK p.Met1fs (c.1dup)?

DOLK p.Met1fs (c.1dup) is associated with Cardiovascular phenotype, DK1-congenital disorder of glycosylation (ClinVar).

How common is DOLK p.Met1fs (c.1dup) in the general population?

DOLK p.Met1fs (c.1dup) is rare (popmax 0.881%, nfe) (gnomAD).

DOLK p.Met1fs

c.1dup · rs531969689 · VCV167006

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.881%, nfe)

Conditions

Cardiovascular phenotype

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 11	GERP 1.9, phastCons 1
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.881% European (non-Finnish) · 10,399/1,179,958 alleles

Filtering AF 0.867% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.861%

Overall 0.723% 11,652/1,612,158 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.881%	113
Finnishnot grpmax-eligible	0.841%	119
Remaining individualsnot grpmax-eligible	0.555%	180
Admixed American	0.247%	405
Ashkenazi Jewishnot grpmax-eligible	0.155%	644
African / African-American	0.139%	721
Middle Eastern	0.137%	728
South Asian	0.0747%	1,339
East Asian	0.00223%	44,832

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: DOLK
Protein: p.Met1fs
Coding: c.1dup
MANE Select: NM_014908
dbSNP: rs531969689
Type: Duplication
Location: chr9:128947302 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.37

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: DK1-congenital disorder of glycosylation

Similar variants

DOLK p.Met1Ile Pathogenic/Likely pathogenic ★★ same residue
DOLK p.Met1Thr Pathogenic/Likely pathogenic ★★ same residue
DOLK p.Ile371fs Likely pathogenic ★ same condition
DOLK p.Asp494Ter Uncertain significance ★ same condition
DOLK p.Leu198fs Uncertain significance ★ same condition
DOLK p.Leu445fs Conflicting classifications of pathogenicity ★ same condition
DOLK p.Val449_Gly450insVal Uncertain significance ★ same condition
DOLK p.His408Asp Pathogenic/Likely pathogenic ★★ 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-met1fs (accessed [today's date]).

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