Is AK2 p.Ala32Thr (c.94G>A) pathogenic?

AK2 p.Ala32Thr (c.94G>A) is classified Uncertain significance in AK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-07). AlphaMissense: likely pathogenic (0.9566); Ultra-rare (popmax 0.0267%, eas); Associated with Inborn genetic diseases.

What condition is associated with AK2 p.Ala32Thr (c.94G>A)?

AK2 p.Ala32Thr (c.94G>A) is associated with Inborn genetic diseases, reticular dysgenesis (ClinVar).

How common is AK2 p.Ala32Thr (c.94G>A) in the general population?

AK2 p.Ala32Thr (c.94G>A) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

What do computational predictors say about AK2 p.Ala32Thr (c.94G>A)?

AlphaMissense predicts likely pathogenic (score 0.9566) — an in-silico prediction, not a clinical call.

AK2 p.Ala32Thr

c.94G>A · rs779260498 · VCV660097

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9566 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9566	likely pathogenic
REVEL	0.854	moderately pathogenic-leaning
SaProt	LLR -5.88	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 24 kb · p 0.0069 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.0267% East Asian · 12/44,894 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00124% 20/1,614,018 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,741
Remaining individualsnot grpmax-eligible	0.0112%	8,926
South Asian	0.0011%	91,082

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: AK2
Protein: p.Ala32Thr
Coding: c.94G>A
MANE Select: NM_001625
dbSNP: rs779260498
Type: single nucleotide variant
Location: chr1:33024567 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.49 · 3 PDB
Residue 32: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: reticular dysgenesis

Similar variants

AK2 c.330+5G>A Pathogenic ★★ same condition
AK2 c.498+1G>A Pathogenic/Likely pathogenic ★★ same condition
AK2 p.Ala182Asp 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-ala32thr (accessed [today's date]).

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