Is AAR2 p.Arg90Cys (c.268C>T) pathogenic?

AAR2 p.Arg90Cys (c.268C>T) is classified Uncertain significance in AAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-11). AlphaMissense: likely benign (0.1184); Rare (popmax 0.121%, sas).

How common is AAR2 p.Arg90Cys (c.268C>T) in the general population?

AAR2 p.Arg90Cys (c.268C>T) is rare (popmax 0.121%, sas) (gnomAD).

What do computational predictors say about AAR2 p.Arg90Cys (c.268C>T)?

AlphaMissense predicts likely benign (score 0.1184) — an in-silico prediction, not a clinical call.

AAR2 p.Arg90Cys

c.268C>T · rs548506013 · VCV3134564

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1184 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.121%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1184	likely benign
REVEL	0.297	indeterminate
SaProt	LLR -12.00	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 16 kb · p 0.0057 · regional, not allelic
Overall
CADD	28.0	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 0.121% South Asian · 110/91,086 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0956%

Overall 0.00991% 160/1,614,178 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.121%	828
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0112%	8,930
European (non-Finnish)	0.00322%	31,053
East Asian	0.00223%	44,872
Finnishnot grpmax-eligible	0.00156%	64,028
African / African-American	0.00133%	75,042

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: AAR2
Protein: p.Arg90Cys
Coding: c.268C>T
MANE Select: NM_001271874
dbSNP: rs548506013
Type: single nucleotide variant
Location: chr20:36240136 (GRCh38)
Gene constraint: LOEUF 1.472 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.74 · 1 PDB
Residue 90: a β-strand

Full AAR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AAR2 p.Ala365Thr Likely benign ★★ same type
AAR2 p.Ala128Thr Uncertain significance ★ ⚠ same type
AAR2 p.Ala235Thr Uncertain significance ★ ⚠ same type
AAR2 p.Ala371Asp Uncertain significance ★ ⚠ same type
AAR2 p.Ala371Val Uncertain significance ★ ⚠ same type
AAR2 p.Arg13His Uncertain significance ★ ⚠ same type
AAR2 p.Arg173His Uncertain significance ★ ⚠ same type
AAR2 p.Arg180Cys 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/aar2-p-arg90cys (accessed [today's date]).

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