Is AIMP2 p.Thr154= (c.462G>T) pathogenic?

AIMP2 p.Thr154= (c.462G>T) is classified Benign/Likely benign in AIMP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-21). Low-frequency (popmax 2.85%, afr); Associated with leukodystrophy, hypomyelinating, 17.

What condition is associated with AIMP2 p.Thr154= (c.462G>T)?

AIMP2 p.Thr154= (c.462G>T) is associated with leukodystrophy, hypomyelinating, 17 (ClinVar).

How common is AIMP2 p.Thr154= (c.462G>T) in the general population?

AIMP2 p.Thr154= (c.462G>T) is low-frequency (popmax 2.85%, afr) (gnomAD).

AIMP2 p.Thr154=

c.462G>T · rs61735883 · VCV711475

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.85%, afr)

Conditions

leukodystrophy, hypomyelinating, 17

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 -8.9
Overall
CADD	0.031	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.85% African / African-American · 2,134/74,922 alleles

Filtering AF 2.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.71%

Overall 0.146% 2,349/1,613,938 alleles · low-frequency exomes 1,164/1,461,880 · genomes 1,185/152,058 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.85%	35
Admixed American	0.162%	618
Remaining individualsnot grpmax-eligible	0.142%	702
Middle Eastern	0.033%	3,031
South Asian	0.00439%	22,768
European (non-Finnish)	0.00195%	51,305

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.Thr154=
Coding: c.462G>T
MANE Select: NM_006303
dbSNP: rs61735883
Type: single nucleotide variant
Location: chr7:6017933 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.65 · 13 PDB
Residue 154: the 'interaction with prkn' region; a β-strand; a UniProt-annotated variant site (in hld17)

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.Thr154Met Uncertain significance ★★ ⚠ same residue
AIMP2 p.Tyr35Ter Likely pathogenic ★★ same condition
AIMP2 p.Val6Leu Benign/Likely benign ★★ same condition
AIMP2 p.Tyr25Cys Likely pathogenic ★ ⚠ same condition
AIMP2 p.Gln45= Uncertain significance ★ same condition
AIMP2 p.Met24Arg Uncertain significance ★ ⚠ same condition
AIMP2 p.Met24fs Pathogenic/Likely pathogenic ★★ same condition
AIMP2 p.Ser219fs 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-thr154 (accessed [today's date]).

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