Is AARS1 p.Arg633fs (c.1897del) pathogenic?

AARS1 p.Arg633fs (c.1897del) is classified Likely pathogenic in AARS1 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 0.0011%, sas); Associated with developmental and epileptic encephalopathy, 29.

What condition is associated with AARS1 p.Arg633fs (c.1897del)?

AARS1 p.Arg633fs (c.1897del) is associated with developmental and epileptic encephalopathy, 29 (ClinVar).

How common is AARS1 p.Arg633fs (c.1897del) in the general population?

AARS1 p.Arg633fs (c.1897del) is very rare (popmax 0.0011%, sas) (gnomAD).

AARS1 p.Arg633fs

Q: How is Non-specific early-onset epileptic encephalopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1897del · rs2152154412 · VCV1331683

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

developmental and epileptic encephalopathy, 29

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 1.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Overall 6.84e-05% 1/1,461,890 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.Arg633fs
Coding: c.1897del
MANE Select: NM_001605
dbSNP: rs2152154412
Type: Deletion
Location: chr16:70259075 (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

developmental and epileptic encephalopathy, 29 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal

Similar variants

AARS1 p.Arg633Cys Uncertain significance ★★ ⚠ same residue
AARS1 p.Phe636fs Pathogenic ★ same condition
AARS1 p.Arg633His Uncertain significance ★ ⚠ same residue
AARS1 p.Arg330Ter Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Ala78Ser Uncertain significance ★★ ⚠ same condition
AARS1 p.Arg296Gln Uncertain significance ★★ ⚠ same condition
AARS1 p.Arg320His Uncertain significance ★★ ⚠ same condition
AARS1 p.Arg750Trp Uncertain significance ★★ ⚠ 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-arg633fs (accessed [today's date]).

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