Is FARS2 p.Asp142fs (c.425del) pathogenic?

FARS2 p.Asp142fs (c.425del) is classified Pathogenic in FARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-05). No gnomAD frequency available for this variant; Associated with combined oxidative phosphorylation defect type 14.

What condition is associated with FARS2 p.Asp142fs (c.425del)?

FARS2 p.Asp142fs (c.425del) is associated with combined oxidative phosphorylation defect type 14 (ClinVar).

How common is FARS2 p.Asp142fs (c.425del) in the general population?

FARS2 p.Asp142fs (c.425del) is no gnomAD frequency available for this variant (gnomAD).

FARS2 p.Asp142fs

Q: How is Combined oxidative phosphorylation defect type 14 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.425del · rs2127643855 · VCV1375428

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

Conditions

combined oxidative phosphorylation defect type 14

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 2 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.7	GERP 0.64, phastCons 1

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: FARS2
Protein: p.Asp142fs
Coding: c.425del
MANE Select: NM_006567
dbSNP: rs2127643855
Type: Deletion
Location: chr6:5368995 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.17 · 9 PDB
Residue 142: a UniProt-annotated variant site (in spg77; resulted in severely impaired phenylalanine-trna ligase activity); a turn

Full FARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined oxidative phosphorylation defect type 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined oxidative phosphorylation defect type 14 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

FARS2 p.Asp142Asn Likely pathogenic ★ ⚠ same residue
FARS2 p.Asp142Gly Likely pathogenic ★ same residue
FARS2 p.Asp142Glu Uncertain significance ★ same residue
FARS2 p.Asp265fs Pathogenic/Likely pathogenic ★★ same condition
FARS2 p.Leu316fs Pathogenic/Likely pathogenic ★★ same condition
FARS2 p.Gly390_Asp391del Uncertain significance ★★ same condition
FARS2 p.Arg318fs Likely pathogenic ★ same condition
FARS2 p.Asp142Tyr Pathogenic ★ same residue

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/fars2-p-asp142fs (accessed [today's date]).

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