Is DOLK p.Ala122Pro (c.364G>C) pathogenic?

DOLK p.Ala122Pro (c.364G>C) is classified Uncertain significance in DOLK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-28). AlphaMissense: likely pathogenic (0.9146); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with DOLK p.Ala122Pro (c.364G>C)?

DOLK p.Ala122Pro (c.364G>C) is associated with Cardiovascular phenotype (ClinVar).

How common is DOLK p.Ala122Pro (c.364G>C) in the general population?

DOLK p.Ala122Pro (c.364G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOLK p.Ala122Pro (c.364G>C)?

AlphaMissense predicts likely pathogenic (score 0.9146) — an in-silico prediction, not a clinical call.

DOLK p.Ala122Pro

c.364G>C · VCV4244189

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9146 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9146	likely pathogenic
REVEL	0.607	indeterminate
SaProt	LLR -10.09	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 1,613 bp · p 0.00089 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Ala122Pro
Coding: c.364G>C
MANE Select: NM_014908
Type: single nucleotide variant
Location: chr9:128946940 (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

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-ala122pro (accessed [today's date]).

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