Is DOLK p.Ala482Val (c.1445C>T) pathogenic?

DOLK p.Ala482Val (c.1445C>T) is classified Uncertain significance in DOLK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-13). AlphaMissense: ambiguous (0.5068); Very rare (popmax 0.00878%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DOLK p.Ala482Val (c.1445C>T)?

DOLK p.Ala482Val (c.1445C>T) is associated with Cardiovascular phenotype, DK1-congenital disorder of glycosylation (ClinVar).

How common is DOLK p.Ala482Val (c.1445C>T) in the general population?

DOLK p.Ala482Val (c.1445C>T) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about DOLK p.Ala482Val (c.1445C>T)?

AlphaMissense predicts ambiguous (score 0.5068) — an in-silico prediction, not a clinical call.

DOLK p.Ala482Val

c.1445C>T · rs767693634 · VCV1352727

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5068 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.5068	ambiguous
REVEL	0.462	indeterminate
SaProt	LLR -9.77	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 1,613 bp · p 0.00089 · regional, not allelic
Overall
CADD	28.2	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

Grpmax group 0.00878% South Asian · 8/91,090 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00118% 19/1,614,070 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,386
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Admixed American	0.00167%	59,992
European (non-Finnish)	0.000678%	147,505

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.Ala482Val
Coding: c.1445C>T
MANE Select: NM_014908
dbSNP: rs767693634
Type: single nucleotide variant
Location: chr9:128945859 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.37
Residue 482: a UniProt-annotated variant site (in cdg1m)

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.Ala482= Likely benign ★ 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
DOLK p.Ala115Val 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-ala482val (accessed [today's date]).

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