Is AIMP2 p.Val6Leu (c.16G>C) pathogenic?

AIMP2 p.Val6Leu (c.16G>C) is classified Benign/Likely benign in AIMP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-24). AlphaMissense: likely benign (0.3354); Rare (popmax 0.563%, mid); Associated with leukodystrophy, hypomyelinating, 17.

What condition is associated with AIMP2 p.Val6Leu (c.16G>C)?

AIMP2 p.Val6Leu (c.16G>C) is associated with leukodystrophy, hypomyelinating, 17 (ClinVar).

How common is AIMP2 p.Val6Leu (c.16G>C) in the general population?

AIMP2 p.Val6Leu (c.16G>C) is rare (popmax 0.563%, mid) (gnomAD).

What do computational predictors say about AIMP2 p.Val6Leu (c.16G>C)?

AlphaMissense predicts likely benign (score 0.3354) — an in-silico prediction, not a clinical call.

AIMP2 p.Val6Leu

c.16G>C · rs139842556 · VCV444713

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3354 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.563%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

leukodystrophy, hypomyelinating, 17

Computational evidence

Protein change
AlphaMissense	0.3354	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.54	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 14 kb · p 8e-07 · regional, not allelic
Overall
CADD	24.7	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 0.563% Middle Eastern · 25/4,442 alleles

Filtering AF 0.391% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.334%

Overall 0.0821% 1,323/1,611,826 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.675%	148
Middle Easterngrpmax	0.563%	178
Remaining individualsnot grpmax-eligible	0.173%	577
South Asian	0.101%	989
European (non-Finnish)	0.0725%	1,380
Admixed American	0.0533%	1,876
African / African-American	0.0133%	7,500
East Asian	0.00223%	44,864

Ashkenazi Jewish 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.Val6Leu
Coding: c.16G>C
MANE Select: NM_006303
dbSNP: rs139842556
Type: single nucleotide variant
Location: chr7:6009379 (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.Tyr35Ter Likely pathogenic ★★ same condition
AIMP2 p.Thr154= 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-val6leu (accessed [today's date]).

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