Is AARS1 p.Ala201Pro (c.601G>C) pathogenic?

AARS1 p.Ala201Pro (c.601G>C) is classified Uncertain significance in AARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-15). AlphaMissense: likely pathogenic (0.5755); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with AARS1 p.Ala201Pro (c.601G>C)?

AARS1 p.Ala201Pro (c.601G>C) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is AARS1 p.Ala201Pro (c.601G>C) in the general population?

AARS1 p.Ala201Pro (c.601G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AARS1 p.Ala201Pro (c.601G>C)?

AlphaMissense predicts likely pathogenic (score 0.5755) — an in-silico prediction, not a clinical call.

AARS1 p.Ala201Pro

c.601G>C · rs760716722 · VCV1682301

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5755 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
AlphaMissense	0.5755	likely pathogenic
REVEL	0.251	benign-leaning
SaProt	LLR -12.48	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 30 kb · p 0.25 · regional, not allelic
Overall
CADD	21.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AARS1
Protein: p.Ala201Pro
Coding: c.601G>C
MANE Select: NM_001605
dbSNP: rs760716722
Type: single nucleotide variant
Location: chr16:70271851 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 90.66 · 10 PDB
Residue 201: an α-helix

Full AARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AARS1 p.Ala201Thr Uncertain significance ★★ ⚠ same residue
AARS1 p.Ala201Gly Uncertain significance ★ ⚠ same residue
AARS1 p.Ala201Ser Uncertain significance ★ ⚠ same residue
AARS1 p.Ala201Val Uncertain significance ★ ⚠ same residue
AARS1 c.2177+1G>A Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg13Ter Pathogenic ★★ same condition
AARS1 p.Arg246Ter Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg329Cys Likely pathogenic ★★ 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/aars1-p-ala201pro (accessed [today's date]).

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