Is ADCK2 p.Pro622= (c.1866A>T) pathogenic?

ADCK2 p.Pro622= (c.1866A>T) is classified Likely benign in ADCK2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-11-11). Rare (popmax 0.397%, amr); Associated with ADCK2-related disorder.

What condition is associated with ADCK2 p.Pro622= (c.1866A>T)?

ADCK2 p.Pro622= (c.1866A>T) is associated with ADCK2-related disorder (ClinVar).

How common is ADCK2 p.Pro622= (c.1866A>T) in the general population?

ADCK2 p.Pro622= (c.1866A>T) is rare (popmax 0.397%, amr) (gnomAD).

ADCK2 p.Pro622=

c.1866A>T · rs191492791 · VCV3053428

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.397%, amr)

Conditions

ADCK2-related disorder

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 0.017	GERP 0.97
Overall
CADD	2.109	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.397% Admixed American · 238/59,904 alleles

Filtering AF 0.356% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.34%

Overall 0.0163% 263/1,613,254 alleles · rare exomes 216/1,460,976 · genomes 47/152,278 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.397%	252
Remaining individualsnot grpmax-eligible	0.0144%	6,940
African / African-American	0.0133%	7,503
European (non-Finnish)	0.000509%	196,601

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.Pro622=
Coding: c.1866A>T
MANE Select: NM_052853
dbSNP: rs191492791
Type: single nucleotide variant
Location: chr7:140694788 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.45
Residue 622: a UniProt-annotated variant site (in); 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

Disease context

ADCK2-related disorder

Similar variants

ADCK2 p.Ala137Val Likely benign same condition
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

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-pro622 (accessed [today's date]).

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