Is AIMP2 p.Val148Ile (c.442G>A) pathogenic?

AIMP2 p.Val148Ile (c.442G>A) is classified Benign in AIMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). AlphaMissense: likely benign (0.1186); Low-frequency (popmax 1.04%, sas).

How common is AIMP2 p.Val148Ile (c.442G>A) in the general population?

AIMP2 p.Val148Ile (c.442G>A) is low-frequency (popmax 1.04%, sas) (gnomAD).

What do computational predictors say about AIMP2 p.Val148Ile (c.442G>A)?

AlphaMissense predicts likely benign (score 0.1186) — an in-silico prediction, not a clinical call.

AIMP2 p.Val148Ile

c.442G>A · rs549852720 · VCV2200998

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1186 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.04%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1186	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -9.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 14 kb · p 8e-07 · regional, not allelic
Overall
CADD	19.68	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 1.04% South Asian · 949/91,084 alleles

Filtering AF 0.987% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.965%

Overall 0.0613% 989/1,614,080 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.04%	96
Remaining individualsnot grpmax-eligible	0.056%	1,786
Middle Eastern	0.0165%	6,062
African / African-American	0.00133%	75,012
European (non-Finnish)	0.000254%	393,342

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.Val148Ile
Coding: c.442G>A
MANE Select: NM_006303
dbSNP: rs549852720
Type: single nucleotide variant
Location: chr7:6017913 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.65 · 13 PDB
Residue 148: 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

Similar variants

PMS2 c.-2146C>A Benign ★★★ same type
PMS2 c.-2559T>A Benign ★★★ same type
PMS2 c.-323G>T Benign ★★★ same type
AIMP2 p.Tyr35Ter Likely pathogenic ★★ same type
AIMP2 p.Ala240Val Uncertain significance ★★ ⚠ same type
AIMP2 p.Arg215Cys Uncertain significance ★★ ⚠ same type
AIMP2 p.Arg215His Uncertain significance ★★ ⚠ same type
AIMP2 p.Arg33Lys Uncertain significance ★★ ⚠ 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-val148ile (accessed [today's date]).

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