Is AARS1 p.Ser188Leu (c.562_563inv) pathogenic?

AARS1 p.Ser188Leu (c.562563inv) is classified Pathogenic in AARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-05). Associated with developmental and epileptic encephalopathy, 29.

What condition is associated with AARS1 p.Ser188Leu (c.562_563inv)?

AARS1 p.Ser188Leu (c.562_563inv) is associated with developmental and epileptic encephalopathy, 29 (ClinVar).

AARS1 p.Ser188Leu

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.562_563inv · VCV1164093

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

developmental and epileptic encephalopathy, 29

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 30 kb · p 0.25 · regional, not allelic

Variant & gene context

Gene: AARS1
Protein: p.Ser188Leu
Coding: c.562_563inv
MANE Select: NM_001605
Type: Inversion
Location: chr16:70271889 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 90.66 · 10 PDB
Residue 188: a β-strand

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.Ser188Asn 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
AARS1 p.Asn657Asp Uncertain significance ★★ ⚠ same condition
AARS1 p.Asp87Asn 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-ser188leu (accessed [today's date]).

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