Is AIMP2 p.Arg65Cys (c.193C>T) pathogenic?

AIMP2 p.Arg65Cys (c.193C>T) is classified Conflicting classifications of pathogenicity in AIMP2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-02). AlphaMissense: likely benign (0.1094); Rare (popmax 0.759%, mid); Associated with Inborn genetic diseases.

What condition is associated with AIMP2 p.Arg65Cys (c.193C>T)?

AIMP2 p.Arg65Cys (c.193C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AIMP2 p.Arg65Cys (c.193C>T) in the general population?

AIMP2 p.Arg65Cys (c.193C>T) is rare (popmax 0.759%, mid) (gnomAD).

What do computational predictors say about AIMP2 p.Arg65Cys (c.193C>T)?

AlphaMissense predicts likely benign (score 0.1094) — an in-silico prediction, not a clinical call.

AIMP2 p.Arg65Cys

c.193C>T · rs140850823 · VCV1468614

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1094 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.759%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1094	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.60	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 6	phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 14 kb · p 8e-07 · regional, not allelic
Overall
CADD	26.4	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 0.759% Middle Eastern · 46/6,060 alleles

Filtering AF 0.585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.523%

Overall 0.0468% 756/1,614,124 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.759%	132
Ashkenazi Jewishnot grpmax-eligible	0.122%	822
Remaining individualsnot grpmax-eligible	0.0864%	1,158
Admixed American	0.05%	2,000
European (non-Finnish)	0.0464%	2,157
South Asian	0.0307%	3,253
African / African-American	0.016%	6,252
Finnishnot grpmax-eligible	0.00469%	21,337

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.Arg65Cys
Coding: c.193C>T
MANE Select: NM_006303
dbSNP: rs140850823
Type: single nucleotide variant
Location: chr7:6015203 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.65 · 13 PDB
Residue 65: 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-arg65cys (accessed [today's date]).

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