Is AAR2 p.Asp7Ala (c.20A>C) pathogenic?

AAR2 p.Asp7Ala (c.20A>C) is classified Uncertain significance in AAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: likely benign (0.3029); Very rare (popmax 8.54e-05%, nfe).

How common is AAR2 p.Asp7Ala (c.20A>C) in the general population?

AAR2 p.Asp7Ala (c.20A>C) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

What do computational predictors say about AAR2 p.Asp7Ala (c.20A>C)?

AlphaMissense predicts likely benign (score 0.3029) — an in-silico prediction, not a clinical call.

AAR2 p.Asp7Ala

c.20A>C · VCV3824881

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3029 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3029	likely benign
REVEL	0.571	indeterminate
SaProt	LLR -13.19	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 9.3	GERP 2.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 16 kb · p 0.0057 · regional, not allelic
Overall
CADD	26.1	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 8.54e-05% European (non-Finnish) · 1/1,170,330 alleles

Overall 0.000657% 1/152,182 alleles · very rare

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.Asp7Ala
Coding: c.20A>C
MANE Select: NM_001271874
Type: single nucleotide variant
Location: chr20:36239888 (GRCh38)
Gene constraint: LOEUF 1.472 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.74 · 1 PDB

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-asp7ala (accessed [today's date]).

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