Is AARS1 p.Asp790Val (c.2369A>T) pathogenic?

AARS1 p.Asp790Val (c.2369A>T) is classified Benign in AARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-04). AlphaMissense: likely benign (0.0928); Rare (popmax 0.47%, sas); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with AARS1 p.Asp790Val (c.2369A>T)?

AARS1 p.Asp790Val (c.2369A>T) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is AARS1 p.Asp790Val (c.2369A>T) in the general population?

AARS1 p.Asp790Val (c.2369A>T) is rare (popmax 0.47%, sas) (gnomAD).

What do computational predictors say about AARS1 p.Asp790Val (c.2369A>T)?

AlphaMissense predicts likely benign (score 0.0928) — an in-silico prediction, not a clinical call.

AARS1 p.Asp790Val

c.2369A>T · rs555357914 · VCV1682136

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0928 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.47%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
AlphaMissense	0.0928	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -7.18	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.26	donor gain · deltas
Constraint at this position
Conservation	phyloP 6.1	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 30 kb · p 0.25 · regional, not allelic
Overall
CADD	23.1	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 0.47% South Asian · 428/91,086 alleles

Filtering AF 0.433% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.419%

Overall 0.0269% 434/1,614,010 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.47%	213
Remaining individualsnot grpmax-eligible	0.008%	12,501
European (non-Finnish)	8.48e-05%	1,179,903

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.Asp790Val
Coding: c.2369A>T
MANE Select: NM_001605
dbSNP: rs555357914
Type: single nucleotide variant
Location: chr16:70254652 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 90.66 · 10 PDB
Residue 790: 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.Asp790Tyr 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-asp790val (accessed [today's date]).

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