Is DOLK p.His341= (c.1023C>T) pathogenic?

DOLK p.His341= (c.1023C>T) is classified Likely benign in DOLK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-20). Very rare (popmax 0.00102%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DOLK p.His341= (c.1023C>T)?

DOLK p.His341= (c.1023C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is DOLK p.His341= (c.1023C>T) in the general population?

DOLK p.His341= (c.1023C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

DOLK p.His341=

c.1023C>T · VCV3842086

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.172	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.66, phastCons 1
Overall
CADD	6.294	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,180,044 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000743% 12/1,614,022 alleles · very rare

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.His341=
Coding: c.1023C>T
MANE Select: NM_014908
Type: single nucleotide variant
Location: chr9:128946281 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.37
Residue 341: 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

Similar variants

DOLK p.Met1Thr Pathogenic/Likely pathogenic ★★ same condition
DOLK p.Ala194Val Uncertain significance ★★ ⚠ same condition
DOLK p.Ala25Thr Uncertain significance ★★ ⚠ same condition
DOLK p.Ala363Thr Uncertain significance ★★ ⚠ same condition
DOLK p.Ala435Pro Uncertain significance ★★ ⚠ same condition
DOLK p.Ala482Val Uncertain significance ★★ ⚠ same condition
DOLK p.Ala504Thr Uncertain significance ★★ ⚠ same condition
DOLK p.Arg109Ser 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-his341 (accessed [today's date]).

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