Is DOLK p.Ala308= (c.924C>T) pathogenic?

DOLK p.Ala308= (c.924C>T) is classified Likely benign in DOLK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-21). Ultra-rare (popmax 0.0512%, eas); Associated with Cardiovascular phenotype.

What condition is associated with DOLK p.Ala308= (c.924C>T)?

DOLK p.Ala308= (c.924C>T) is associated with Cardiovascular phenotype, DK1-congenital disorder of glycosylation (ClinVar).

How common is DOLK p.Ala308= (c.924C>T) in the general population?

DOLK p.Ala308= (c.924C>T) is ultra-rare (popmax 0.0512%, eas) (gnomAD).

DOLK p.Ala308=

c.924C>T · rs531714647 · VCV1663889

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0512%, eas)

Conditions

Cardiovascular phenotype

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 3.4	GERP -0.76, phastCons 1
Overall
CADD	8.638	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0512% East Asian · 23/44,880 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.00155% 25/1,614,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0512%	1,951
Remaining individualsnot grpmax-eligible	0.0032%	31,253

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.Ala308=
Coding: c.924C>T
MANE Select: NM_014908
dbSNP: rs531714647
Type: single nucleotide variant
Location: chr9:128946380 (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.Ala308Thr 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
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-ala308 (accessed [today's date]).

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