Is AIMP2 p.Met24fs (c.72_73del) pathogenic?

AIMP2 p.Met24fs (c.7273del) is classified Pathogenic/Likely pathogenic in AIMP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-03). Very rare (popmax 0.0017%, nfe); Associated with leukodystrophy, hypomyelinating, 17.

What condition is associated with AIMP2 p.Met24fs (c.72_73del)?

AIMP2 p.Met24fs (c.72_73del) is associated with leukodystrophy, hypomyelinating, 17 (ClinVar).

How common is AIMP2 p.Met24fs (c.72_73del) in the general population?

AIMP2 p.Met24fs (c.72_73del) is very rare (popmax 0.0017%, nfe) (gnomAD).

AIMP2 p.Met24fs

c.72_73del · rs1786357576 · VCV985778

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0017%, nfe)

Conditions

leukodystrophy, hypomyelinating, 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0017% European (non-Finnish) · 20/1,179,904 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00158% 23/1,458,998 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00482%	20,766
European (non-Finnish)grpmax	0.0017%	58,995

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: AIMP2
Protein: p.Met24fs
Coding: c.72_73del
MANE Select: NM_006303
dbSNP: rs1786357576
Type: Deletion
Location: chr7:6009434 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.65 · 13 PDB

Full AIMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

leukodystrophy, hypomyelinating, 17 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AIMP2 p.Met24Arg Uncertain significance ★ ⚠ same residue
AIMP2 p.Met24Ile Uncertain significance ★ ⚠ same residue
AIMP2 p.Met24Thr Uncertain significance ★ ⚠ same residue
AIMP2 p.Ser219fs Likely pathogenic ★★ same condition
AIMP2 p.Tyr35Ter Likely pathogenic ★★ same condition
AIMP2 p.Thr154= Benign/Likely benign ★★ same condition
AIMP2 p.Val6Leu Benign/Likely benign ★★ same condition
AIMP2 p.Tyr25Cys Likely pathogenic ★ ⚠ 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/aimp2-p-met24fs (accessed [today's date]).

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