Is GARS1 p.Val71Ala (c.212T>C) pathogenic?

GARS1 p.Val71Ala (c.212T>C) is classified Uncertain significance in GARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-25). AlphaMissense: likely pathogenic (0.8917); No allele count reported in gnomAD v4.1 (AN 1,537,978); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with GARS1 p.Val71Ala (c.212T>C)?

GARS1 p.Val71Ala (c.212T>C) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is GARS1 p.Val71Ala (c.212T>C) in the general population?

GARS1 p.Val71Ala (c.212T>C) is no allele count reported in gnomAD v4.1 (AN 1,537,978) (gnomAD).

What do computational predictors say about GARS1 p.Val71Ala (c.212T>C)?

AlphaMissense predicts likely pathogenic (score 0.8917) — an in-silico prediction, not a clinical call.

GARS1 p.Val71Ala

c.212T>C · rs2534281070 · VCV3022343

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8917 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,537,978)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
AlphaMissense	0.8917	likely pathogenic
REVEL	0.216	benign-leaning
SaProt	LLR -11.46	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 5,108 bp · p 0.097 · regional, not allelic
Overall
CADD	26.0	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

No allele count reported in gnomAD v4.1 (AN 1,537,978). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GARS1
Protein: p.Val71Ala
Coding: c.212T>C
MANE Select: NM_002047
dbSNP: rs2534281070
Type: single nucleotide variant
Location: chr7:30595133 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 14 PDB
Residue 71: the whep-trs domain; an α-helix

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

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GARS1 p.Asp200Asn Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.Gly294Arg Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.Gly339Arg Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.His472Arg Pathogenic ★★ same condition
GARS1 p.Ile334Asn Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.Ile334Phe Pathogenic ★★ same condition
GARS1 p.Ile334Thr Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.Ser265Phe Pathogenic/Likely pathogenic ★★ 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/gars1-p-val71ala (accessed [today's date]).

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