Is AK2 p.Ala182Asp (c.545C>A) pathogenic?

AK2 p.Ala182Asp (c.545C>A) is classified Pathogenic/Likely pathogenic in AK2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-23). AlphaMissense: likely pathogenic (0.9257); Absent from gnomAD v4.1; Associated with AK2-related disorder.

What condition is associated with AK2 p.Ala182Asp (c.545C>A)?

AK2 p.Ala182Asp (c.545C>A) is associated with AK2-related disorder, reticular dysgenesis (ClinVar).

How common is AK2 p.Ala182Asp (c.545C>A) in the general population?

AK2 p.Ala182Asp (c.545C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AK2 p.Ala182Asp (c.545C>A)?

AlphaMissense predicts likely pathogenic (score 0.9257) — an in-silico prediction, not a clinical call.

AK2 p.Ala182Asp

c.545C>A · rs559947967 · VCV190980

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9257 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

AK2-related disorder

Computational evidence

Protein change
AlphaMissense	0.9257	likely pathogenic ✓ concordant with ClinVar
REVEL	0.824	moderately pathogenic-leaning
SaProt	LLR -10.12	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 24 kb · p 0.0069 · regional, not allelic
Overall
CADD	29.3	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: AK2
Protein: p.Ala182Asp
Coding: c.545C>A
MANE Select: NM_001625
dbSNP: rs559947967
Type: single nucleotide variant
Location: chr1:33013356 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.49 · 3 PDB
Residue 182: an α-helix

Full AK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AK2-related disorder

Also linked: reticular dysgenesis

Similar variants

AK2 p.Ala182Val Uncertain significance ★ same residue
AK2 c.330+5G>A Pathogenic ★★ same condition
AK2 c.498+1G>A Pathogenic/Likely pathogenic ★★ same condition
AK2 p.Arg103Trp Pathogenic/Likely pathogenic ★★ same condition
AK2 p.Arg175Pro Likely pathogenic ★★ same condition
AK2 p.Met1Val Pathogenic ★★ same condition
AK2 p.Ala212Thr Uncertain significance ★★ ⚠ same condition
AK2 p.Ala2Val 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/ak2-p-ala182asp (accessed [today's date]).

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