Is AIMP2 p.Tyr35Ter (c.105C>A) pathogenic?

AIMP2 p.Tyr35Ter (c.105C>A) is classified Likely pathogenic in AIMP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-06-22). Very rare (popmax 0.00335%, sas); Associated with leukodystrophy, hypomyelinating, 17.

What condition is associated with AIMP2 p.Tyr35Ter (c.105C>A)?

AIMP2 p.Tyr35Ter (c.105C>A) is associated with leukodystrophy, hypomyelinating, 17 (ClinVar).

How common is AIMP2 p.Tyr35Ter (c.105C>A) in the general population?

AIMP2 p.Tyr35Ter (c.105C>A) is very rare (popmax 0.00335%, sas) (gnomAD).

AIMP2 p.Tyr35Ter

c.105C>A · rs529613640 · VCV428589

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00335%, sas)

Conditions

leukodystrophy, hypomyelinating, 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 4
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	phastCons 0.12
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00335% South Asian · 3/89,546 alleles

Filtering AF 0.00089% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000447%

Overall 0.000252% 4/1,590,062 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00335%	29,849
European (non-Finnish)	8.54e-05%	1,171,258

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.Tyr35Ter
Coding: c.105C>A
MANE Select: NM_006303
dbSNP: rs529613640
Type: single nucleotide variant
Location: chr7:6009468 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.65 · 13 PDB
Residue 35: 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.Thr154= Benign/Likely benign ★★ 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
PMS2 c.-2146C>A Benign ★★★ 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/aimp2-p-tyr35ter (accessed [today's date]).

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