Is DOLK p.Ile480Val (c.1438A>G) pathogenic?

DOLK p.Ile480Val (c.1438A>G) is classified Conflicting classifications of pathogenicity in DOLK (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-06-06). AlphaMissense: likely benign (0.0748); Ultra-rare (popmax 0.0333%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DOLK p.Ile480Val (c.1438A>G)?

DOLK p.Ile480Val (c.1438A>G) is associated with Cardiovascular phenotype, DK1-congenital disorder of glycosylation (ClinVar).

How common is DOLK p.Ile480Val (c.1438A>G) in the general population?

DOLK p.Ile480Val (c.1438A>G) is ultra-rare (popmax 0.0333%, amr) (gnomAD).

What do computational predictors say about DOLK p.Ile480Val (c.1438A>G)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

DOLK p.Ile480Val

c.1438A>G · rs144209926 · VCV377266

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.63, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 1,613 bp · p 0.00089 · regional, not allelic
Overall
CADD	15.97	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 0.0333% Admixed American · 20/60,014 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0184%

Overall 0.017% 275/1,614,182 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0333%	3,001
South Asian	0.0209%	4,794
European (non-Finnish)	0.0181%	5,514
East Asian	0.0156%	6,413
African / African-American	0.0107%	9,378
Remaining individualsnot grpmax-eligible	0.0096%	10,419
Finnishnot grpmax-eligible	0.00156%	64,032

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.Ile480Val
Coding: c.1438A>G
MANE Select: NM_014908
dbSNP: rs144209926
Type: single nucleotide variant
Location: chr9:128945866 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.37
Residue 480: 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.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-ile480val (accessed [today's date]).

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