Is AIMP2 p.Arg257Cys (c.769C>T) pathogenic?

AIMP2 p.Arg257Cys (c.769C>T) is classified Uncertain significance in AIMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-19). AlphaMissense: likely benign (0.1003); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with AIMP2 p.Arg257Cys (c.769C>T)?

AIMP2 p.Arg257Cys (c.769C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AIMP2 p.Arg257Cys (c.769C>T) in the general population?

AIMP2 p.Arg257Cys (c.769C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about AIMP2 p.Arg257Cys (c.769C>T)?

AlphaMissense predicts likely benign (score 0.1003) — an in-silico prediction, not a clinical call.

AIMP2 p.Arg257Cys

c.769C>T · VCV4259587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1003 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1003	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -8.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.3	phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 14 kb · p 8e-07 · regional, not allelic
Overall
CADD	23.7	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 0.00439% South Asian · 4/91,088 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000682% 11/1,614,042 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,772
Remaining individualsnot grpmax-eligible	0.0032%	31,243
East Asian	0.00223%	44,898
Admixed American	0.00167%	59,990
European (non-Finnish)	0.000254%	393,337

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.Arg257Cys
Coding: c.769C>T
MANE Select: NM_014413 · reported on NM_006303
Type: single nucleotide variant
Location: chr7:6023497 (GRCh38)

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

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-arg257cys (accessed [today's date]).

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