Is AARS1 p.Thr24Pro (c.70A>C) pathogenic?

AARS1 p.Thr24Pro (c.70A>C) is classified Uncertain significance in AARS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-09-01). AlphaMissense: ambiguous (0.392); Very rare (popmax 0.00178%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AARS1 p.Thr24Pro (c.70A>C)?

AARS1 p.Thr24Pro (c.70A>C) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is AARS1 p.Thr24Pro (c.70A>C) in the general population?

AARS1 p.Thr24Pro (c.70A>C) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about AARS1 p.Thr24Pro (c.70A>C)?

AlphaMissense predicts ambiguous (score 0.392) — an in-silico prediction, not a clinical call.

AARS1 p.Thr24Pro

c.70A>C · rs768158204 · VCV1038409

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.392 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.392	ambiguous
REVEL	0.443	indeterminate
SaProt	LLR -10.39	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 30 kb · p 0.25 · regional, not allelic
Overall
CADD	20.3	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 0.00178% European (non-Finnish) · 21/1,180,030 alleles

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

Overall 0.00144% 21/1,461,886 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: AARS1
Protein: p.Thr24Pro
Coding: c.70A>C
MANE Select: NM_001605
dbSNP: rs768158204
Type: single nucleotide variant
Location: chr16:70282694 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 90.66 · 10 PDB

Full AARS1 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

Also linked: Charcot-Marie-Tooth disease type 2

Similar variants

AARS1 p.Thr24Met Uncertain significance ★★ ⚠ same residue
AARS1 p.Thr24Arg Uncertain significance ★ ⚠ same residue
AARS1 p.Thr24Ser Uncertain significance ★ ⚠ same residue
AARS1 p.Thr24= Likely benign ★ 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-thr24pro (accessed [today's date]).

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