Is AARS1 p.Ile470Val (c.1408A>G) pathogenic?

AARS1 p.Ile470Val (c.1408A>G) is classified Uncertain significance in AARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-13). AlphaMissense: likely benign (0.0973); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AARS1 p.Ile470Val (c.1408A>G)?

AARS1 p.Ile470Val (c.1408A>G) is associated with Inborn genetic diseases (ClinVar).

How common is AARS1 p.Ile470Val (c.1408A>G) in the general population?

AARS1 p.Ile470Val (c.1408A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about AARS1 p.Ile470Val (c.1408A>G)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

AARS1 p.Ile470Val

c.1408A>G · rs879254145 · VCV1800210

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.216	benign-leaning
SaProt	LLR -4.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.72, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 30 kb · p 0.25 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 6.84e-05% 1/1,461,880 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.Ile470Val
Coding: c.1408A>G
MANE Select: NM_001605
dbSNP: rs879254145
Type: single nucleotide variant
Location: chr16:70265042 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AARS1 p.Ile470= Benign/Likely benign ★★ same residue
AARS1 p.Ile470Asn Uncertain significance ★★ ⚠ same residue
AARS1 p.Ile470Phe Uncertain significance ★★ ⚠ same residue
AARS1 p.Ile470Met 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

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-ile470val (accessed [today's date]).

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