Is ADCK2 p.Ala465Val (c.1394C>T) pathogenic?

ADCK2 p.Ala465Val (c.1394C>T) is classified Uncertain significance in ADCK2 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-09-27). AlphaMissense: likely benign (0.0719); Very rare (popmax 0.00892%, eas).

How common is ADCK2 p.Ala465Val (c.1394C>T) in the general population?

ADCK2 p.Ala465Val (c.1394C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about ADCK2 p.Ala465Val (c.1394C>T)?

AlphaMissense predicts likely benign (score 0.0719) — an in-silico prediction, not a clinical call.

ADCK2 p.Ala465Val

c.1394C>T · rs369426384 · VCV3080843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0719 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0719	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -6.55	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 -1.4	GERP -5.5
Regional constraint	o/e 0.87	unconstrained · MANE · 21 kb · p 0.00024 · regional, not allelic
Overall
CADD	5.814	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00892% East Asian · 4/44,868 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00157% 23/1,461,714 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,217
African / African-American	0.00267%	37,519
South Asian	0.0022%	45,534
European (non-Finnish)	0.00127%	78,669

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: ADCK2
Protein: p.Ala465Val
Coding: c.1394C>T
MANE Select: NM_052853
dbSNP: rs369426384
Type: single nucleotide variant
Location: chr7:140687078 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.45
Residue 465: 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.Ala510Thr Uncertain significance ★ ⚠ same type
ADCK2 p.Ala78Ser Uncertain significance ★ ⚠ same type
ADCK2 p.Arg292Trp Uncertain significance ★ ⚠ same type
ADCK2 p.Arg378Trp 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-ala465val (accessed [today's date]).

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