Is GARS1 p.Asp511Val (c.1532A>T) pathogenic?

GARS1 p.Asp511Val (c.1532A>T) is classified Uncertain significance in GARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely benign (0.2437); Absent from gnomAD v4.1.

How common is GARS1 p.Asp511Val (c.1532A>T) in the general population?

GARS1 p.Asp511Val (c.1532A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GARS1 p.Asp511Val (c.1532A>T)?

AlphaMissense predicts likely benign (score 0.2437) — an in-silico prediction, not a clinical call.

GARS1 p.Asp511Val

c.1532A>T · VCV4541271

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2437 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2437	likely benign
REVEL	0.885	moderately pathogenic-leaning
SaProt	LLR -15.10	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 34 kb · p 2.2e-07 · regional, not allelic
Overall
CADD	26.2	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: GARS1
Protein: p.Asp511Val
Coding: c.1532A>T
MANE Select: NM_002047
Type: single nucleotide variant
Location: chr7:30622381 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 14 PDB

Full GARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GARS1 p.Asp511= Conflicting classifications of pathogenicity ★ same residue
GARS1 p.Asp511His Uncertain significance ★ ⚠ same residue
GARS1 p.Asp200Asn Pathogenic/Likely pathogenic ★★ same type
GARS1 p.Gly294Arg Pathogenic/Likely pathogenic ★★ same type
GARS1 p.Gly339Arg Pathogenic/Likely pathogenic ★★ same type
GARS1 p.His472Arg Pathogenic ★★ same type
GARS1 p.Ile334Asn Pathogenic/Likely pathogenic ★★ same type
GARS1 p.Ile334Phe Pathogenic ★★ same type

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/gars1-p-asp511val (accessed [today's date]).

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