Is AARS1 p.Asp359= (c.1077T>C) pathogenic?

AARS1 p.Asp359= (c.1077T>C) is classified Conflicting classifications of pathogenicity in AARS1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2019-07-11). Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with AARS1 p.Asp359= (c.1077T>C)?

AARS1 p.Asp359= (c.1077T>C) is associated with Inborn genetic diseases (ClinVar).

How common is AARS1 p.Asp359= (c.1077T>C) in the general population?

AARS1 p.Asp359= (c.1077T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

AARS1 p.Asp359=

c.1077T>C · rs1319547380 · VCV546774

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Inborn genetic diseases

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 0.63	GERP -2.1, phastCons 0.9
Overall
CADD	7.316	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,916 alleles

Overall 0.000186% 3/1,614,038 alleles · very rare exomes 2/1,461,888 · genomes 1/152,150 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-Americangrpmax	0.00133%	74,916
European (non-Finnish)	8.47e-05%	1,180,038

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp359=
Coding: c.1077T>C
MANE Select: NM_001605
dbSNP: rs1319547380
Type: single nucleotide variant
Location: chr16:70267804 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 90.66 · 10 PDB
Residue 359: a turn

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

Similar variants

AARS1 p.Asp359Asn Uncertain significance ★★ ⚠ same residue
AARS1 p.Asp359Ala Uncertain significance ★ ⚠ same residue
AARS1 p.Asp359Gly Uncertain significance ★ ⚠ same residue
AARS1 c.333+3A>G Uncertain significance ★★ same condition
AARS1 p.Ala201Thr Uncertain significance ★★ ⚠ same condition
AARS1 p.Ala335Thr Uncertain significance ★★ ⚠ same condition
AARS1 p.Ala360Gly Uncertain significance ★★ ⚠ same condition
AARS1 p.Ala614Ser 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-asp359 (accessed [today's date]).

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