Is AIMP2 p.Pro28Arg (c.83C>G) pathogenic?

AIMP2 p.Pro28Arg (c.83C>G) is classified Uncertain significance in AIMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.1762); Very rare (popmax 0.00178%, nfe).

How common is AIMP2 p.Pro28Arg (c.83C>G) in the general population?

AIMP2 p.Pro28Arg (c.83C>G) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about AIMP2 p.Pro28Arg (c.83C>G)?

AlphaMissense predicts likely benign (score 0.1762) — an in-silico prediction, not a clinical call.

AIMP2 p.Pro28Arg

c.83C>G · rs762176789 · VCV2181532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1762 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1762	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -6.88	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 7.6	phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 14 kb · p 8e-07 · regional, not allelic
Overall
CADD	27.1	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 0.00178% European (non-Finnish) · 21/1,179,726 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00137% 22/1,610,584 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00178%	56,178
Admixed American	0.00167%	59,862

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.Pro28Arg
Coding: c.83C>G
MANE Select: NM_006303
dbSNP: rs762176789
Type: single nucleotide variant
Location: chr7:6009446 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.65 · 13 PDB
Residue 28: an α-helix

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-pro28arg (accessed [today's date]).

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