Is AARS2 p.Pro260Arg (c.779C>G) pathogenic?

AARS2 p.Pro260Arg (c.779C>G) is classified Uncertain significance in AARS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-09). AlphaMissense: likely benign (0.1843); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with AARS2 p.Pro260Arg (c.779C>G)?

AARS2 p.Pro260Arg (c.779C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is AARS2 p.Pro260Arg (c.779C>G) in the general population?

AARS2 p.Pro260Arg (c.779C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AARS2 p.Pro260Arg (c.779C>G)?

AlphaMissense predicts likely benign (score 0.1843) — an in-silico prediction, not a clinical call.

AARS2 p.Pro260Arg

c.779C>G · VCV3894764

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1843 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1843	likely benign
REVEL	0.855	moderately pathogenic-leaning
SaProt	LLR -8.00	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 13 kb · p 0.00019 · regional, not allelic
Overall
CADD	27.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AARS2
Protein: p.Pro260Arg
Coding: c.779C>G
MANE Select: NM_020745
Type: single nucleotide variant
Location: chr6:44310414 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.05 · 3 PDB

Full AARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AARS2 p.Ala740Thr Uncertain significance ★★ ⚠ same condition
AARS2 p.Arg769Cys Uncertain significance ★★ ⚠ same condition
AARS2 p.His225Tyr Uncertain significance ★★ ⚠ same condition
AARS2 p.Ile224Leu Uncertain significance ★★ ⚠ same condition
AARS2 p.Ile766Ser Uncertain significance ★★ ⚠ same condition
AARS2 p.Leu118Val Uncertain significance ★★ ⚠ same condition
AARS2 p.Leu538Met Uncertain significance ★★ ⚠ same condition
AARS2 p.Val549Met 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/aars2-p-pro260arg (accessed [today's date]).

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