Is DARS2 p.Glu425fs (c.1272_1273delinsC) pathogenic?

DARS2 p.Glu425fs (c.12721273delinsC) is classified Pathogenic in DARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-02). Absent from gnomAD.

How common is DARS2 p.Glu425fs (c.1272_1273delinsC) in the general population?

DARS2 p.Glu425fs (c.1272_1273delinsC) is absent from gnomAD (gnomAD).

DARS2 p.Glu425fs

c.1272_1273delinsC · rs1553204327 · VCV503692

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -4.5, phastCons 0.78

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: DARS2
Protein: p.Glu425fs
Coding: c.1272_1273delinsC
MANE Select: NM_018122
dbSNP: rs1553204327
Type: Indel
Location: chr1:173850407 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.91 · 1 PDB

Full DARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DARS2 p.Glu425Ter Uncertain significance ★ same residue
DARS2 c.228-21_228-20delinsC Pathogenic ★★ same type
DARS2 c.1675-1256_*115delinsGCAACATTTCGGCAACATTCCAACC Pathogenic ★ same type
DARS2 c.228-22_228-21delinsC Pathogenic ★ same type
DARS2 c.228-21_228-20delinsCC Conflicting classifications of pathogenicity ★ same type
DARS2 c.228-20delinsCC Likely benign ★ same type
DARS2 c.227+28_227+29delinsTT Benign 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/dars2-p-glu425fs (accessed [today's date]).

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