Is ADCK2 p.Val591Ala (c.1772T>C) pathogenic?

ADCK2 p.Val591Ala (c.1772T>C) is classified Uncertain significance in ADCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-31). AlphaMissense: likely pathogenic (0.5816); Absent from gnomAD v4.1.

How common is ADCK2 p.Val591Ala (c.1772T>C) in the general population?

ADCK2 p.Val591Ala (c.1772T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADCK2 p.Val591Ala (c.1772T>C)?

AlphaMissense predicts likely pathogenic (score 0.5816) — an in-silico prediction, not a clinical call.

ADCK2 p.Val591Ala

c.1772T>C · VCV3832919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5816 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5816	likely pathogenic
REVEL	0.276	benign-leaning
SaProt	LLR -8.60	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 3.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 21 kb · p 0.00024 · regional, not allelic
Overall
CADD	26.5	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

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: ADCK2
Protein: p.Val591Ala
Coding: c.1772T>C
MANE Select: NM_052853
Type: single nucleotide variant
Location: chr7:140694694 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.45
Residue 591: the protein kinase domain; a UniProt-annotated variant site (found in a patient with slow and progressive proximal muscle weakness with permanent myalgia both at rest and during muscular exertion which results in permanent disability; uncertain significance; decreased levels of coenzyme q10)

Full ADCK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADCK2 p.Ala217Pro Uncertain significance ★ ⚠ same type
ADCK2 p.Ala293Gly Uncertain significance ★ ⚠ same type
ADCK2 p.Ala293Val Uncertain significance ★ ⚠ same type
ADCK2 p.Ala319Thr Uncertain significance ★ ⚠ same type
ADCK2 p.Ala465Val Uncertain significance ★ ⚠ same type
ADCK2 p.Ala510Thr Uncertain significance ★ ⚠ same type
ADCK2 p.Ala78Ser Uncertain significance ★ ⚠ same type
ADCK2 p.Arg292Trp Uncertain significance ★ ⚠ same type

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/adck2-p-val591ala (accessed [today's date]).

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