Is FASTKD2 p.Ser341fs (c.1021del) pathogenic?

FASTKD2 p.Ser341fs (c.1021del) is classified Pathogenic in FASTKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-05). Absent from gnomAD; Associated with combined oxidative phosphorylation deficiency 44.

What condition is associated with FASTKD2 p.Ser341fs (c.1021del)?

FASTKD2 p.Ser341fs (c.1021del) is associated with combined oxidative phosphorylation deficiency 44 (ClinVar).

How common is FASTKD2 p.Ser341fs (c.1021del) in the general population?

FASTKD2 p.Ser341fs (c.1021del) is absent from gnomAD (gnomAD).

FASTKD2 p.Ser341fs

c.1021del · rs1559360466 · VCV4813513

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 deficiency 44

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 5 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.8	GERP 0.75

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: FASTKD2
Protein: p.Ser341fs
Coding: c.1021del
MANE Select: NM_001136193
dbSNP: rs1559360466
Type: Deletion
Location: chr2:206771921 (GRCh38)
Gene constraint: LOEUF 1.203 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.39
Residue 341: a UniProt-annotated variant site (in coxpd44; decreased mitochondrial large ribosomal subunit assembly); a UniProt-annotated variant site (in coxpd44)

Full FASTKD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined oxidative phosphorylation deficiency 44 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FASTKD2 p.Leu549fs Pathogenic ★★ same condition
FASTKD2 p.Ser160fs Likely pathogenic ★★ same condition
FASTKD2 c.2014-12_2014-11del Likely benign ★★ same condition
FASTKD2 p.Asp500fs Likely pathogenic ★ same condition
FASTKD2 p.Leu166fs Likely pathogenic ★ same condition
FASTKD2 p.Leu513fs Likely pathogenic ★ same condition
FASTKD2 p.Lys475fs Likely pathogenic ★ same condition
FASTKD2 p.Pro180fs 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/fastkd2-p-ser341fs (accessed [today's date]).

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