Is DOLK p.Phe110Leu (c.330T>G) pathogenic?

DOLK p.Phe110Leu (c.330T>G) is classified Uncertain significance in DOLK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-11). AlphaMissense: ambiguous (0.5388); Absent from gnomAD v4.1; Associated with DK1-congenital disorder of glycosylation.

What condition is associated with DOLK p.Phe110Leu (c.330T>G)?

DOLK p.Phe110Leu (c.330T>G) is associated with DK1-congenital disorder of glycosylation (ClinVar).

How common is DOLK p.Phe110Leu (c.330T>G) in the general population?

DOLK p.Phe110Leu (c.330T>G) is absent from gnomAD v4.1 (gnomAD).

How is DK1-CDG inherited?

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

What do computational predictors say about DOLK p.Phe110Leu (c.330T>G)?

AlphaMissense predicts ambiguous (score 0.5388) — an in-silico prediction, not a clinical call.

DOLK p.Phe110Leu

c.330T>G · rs2492005348 · VCV2015854

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5388 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

DK1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.5388	ambiguous
REVEL	0.36	indeterminate
SaProt	LLR -5.30	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.22	GERP -3.8, phastCons 0.33
Regional constraint	o/e 0.87	unconstrained · MANE · 1,613 bp · p 0.00089 · regional, not allelic
Overall
CADD	13.16	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DOLK
Protein: p.Phe110Leu
Coding: c.330T>G
MANE Select: NM_014908
dbSNP: rs2492005348
Type: single nucleotide variant
Location: chr9:128946974 (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

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.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
DOLK p.Ala115Val Uncertain significance ★★ ⚠ same condition
DOLK p.Ala129Ser 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-phe110leu (accessed [today's date]).

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