Is AIMP2 p.Arg257His (c.770G>A) pathogenic?

AIMP2 p.Arg257His (c.770G>A) is classified Uncertain significance in AIMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). AlphaMissense: likely benign (0.1022); Rare (popmax 0.145%, eas); Associated with Inborn genetic diseases.

What condition is associated with AIMP2 p.Arg257His (c.770G>A)?

AIMP2 p.Arg257His (c.770G>A) is associated with Inborn genetic diseases (ClinVar).

How common is AIMP2 p.Arg257His (c.770G>A) in the general population?

AIMP2 p.Arg257His (c.770G>A) is rare (popmax 0.145%, eas) (gnomAD).

What do computational predictors say about AIMP2 p.Arg257His (c.770G>A)?

AlphaMissense predicts likely benign (score 0.1022) — an in-silico prediction, not a clinical call.

AIMP2 p.Arg257His

c.770G>A · rs145632958 · VCV3102978

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1022 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.145%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1022	likely benign
REVEL	0.293	indeterminate
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 14 kb · p 8e-07 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.145% East Asian · 65/44,880 alleles

Filtering AF 0.117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.0052% 84/1,614,120 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.145%	690
Remaining individualsnot grpmax-eligible	0.0064%	15,627
South Asian	0.00439%	22,769
Admixed American	0.00333%	30,003
African / African-American	0.00133%	75,040
European (non-Finnish)	0.000678%	147,500

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.Arg257His
Coding: c.770G>A
MANE Select: NM_006303
dbSNP: rs145632958
Type: single nucleotide variant
Location: chr7:6023498 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.65 · 13 PDB
Residue 257: the gst c-terminal domain; an α-helix; a UniProt-annotated variant site (in hld17)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AIMP2 p.Ala240Val Uncertain significance ★★ ⚠ same condition
AIMP2 p.Arg215Cys Uncertain significance ★★ ⚠ same condition
AIMP2 p.Arg215His Uncertain significance ★★ ⚠ same condition
AIMP2 p.Arg33Lys Uncertain significance ★★ ⚠ same condition
AIMP2 p.Arg58Cys Uncertain significance ★★ ⚠ same condition
AIMP2 p.Arg58His Uncertain significance ★★ ⚠ same condition
AIMP2 p.Asn226Ser Uncertain significance ★★ ⚠ same condition
AIMP2 p.Asn29Lys Uncertain significance ★★ ⚠ 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-arg257his (accessed [today's date]).

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