Is DOLK p.Arg399= (c.1197A>G) pathogenic?

DOLK p.Arg399= (c.1197A>G) is classified Likely benign in DOLK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-06). Ultra-rare (popmax 0.0187%, afr); Associated with DK1-congenital disorder of glycosylation.

What condition is associated with DOLK p.Arg399= (c.1197A>G)?

DOLK p.Arg399= (c.1197A>G) is associated with DK1-congenital disorder of glycosylation (ClinVar).

How common is DOLK p.Arg399= (c.1197A>G) in the general population?

DOLK p.Arg399= (c.1197A>G) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

How is DK1-CDG inherited?

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

DOLK p.Arg399=

c.1197A>G · rs767133437 · VCV1433314

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Conditions

DK1-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -1.8, phastCons 0.004
Overall
CADD	4.863	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,890 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.000929% 15/1,613,970 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,349
Admixed American	0.00167%	59,992

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.Arg399=
Coding: c.1197A>G
MANE Select: NM_014908
dbSNP: rs767133437
Type: single nucleotide variant
Location: chr9:128946107 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.37
Residue 399: 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.Arg399Gln Uncertain significance ★★ ⚠ same residue
DOLK p.Arg399Gly Uncertain significance ★ ⚠ same residue
DOLK p.His408Asp Pathogenic/Likely pathogenic ★★ same condition
DOLK p.Met1Ile Pathogenic/Likely pathogenic ★★ same condition
DOLK p.Met1Thr Pathogenic/Likely pathogenic ★★ same condition
DOLK c.-194G>T Uncertain significance ★★ same condition
DOLK c.-22G>A Uncertain significance ★★ same condition
DOLK c.-269G>T 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-arg399 (accessed [today's date]).

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