Is AARS1 p.Val380= (c.1140G>A) pathogenic?

AARS1 p.Val380= (c.1140G>A) is classified Likely benign in AARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-27). Very rare (popmax 0.00801%, afr); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with AARS1 p.Val380= (c.1140G>A)?

AARS1 p.Val380= (c.1140G>A) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is AARS1 p.Val380= (c.1140G>A) in the general population?

AARS1 p.Val380= (c.1140G>A) is very rare (popmax 0.00801%, afr) (gnomAD).

AARS1 p.Val380=

c.1140G>A · rs149055899 · VCV1117703

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3.4
Overall
CADD	9.154	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,912 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000743% 12/1,614,034 alleles · very rare exomes 2/1,461,888 · genomes 10/152,146 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,485
Admixed American	0.005%	19,997
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000169%	590,016

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.Val380=
Coding: c.1140G>A
MANE Select: NM_001605
dbSNP: rs149055899
Type: single nucleotide variant
Location: chr16:70267741 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 90.66 · 10 PDB
Residue 380: 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.Val380Leu 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
AARS1 p.Arg329His Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg330Ter Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg333Ter Pathogenic/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-val380 (accessed [today's date]).

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