Is PDSS2 p.Ser174fs (c.516_519dup) pathogenic?

PDSS2 p.Ser174fs (c.516519dup) is classified Uncertain significance in PDSS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). Associated with coenzyme Q10 deficiency, primary, 3.

What condition is associated with PDSS2 p.Ser174fs (c.516_519dup)?

PDSS2 p.Ser174fs (c.516_519dup) is associated with coenzyme Q10 deficiency, primary, 3 (ClinVar).

PDSS2 p.Ser174fs

c.516_519dup · VCV4079518

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

coenzyme Q10 deficiency, primary, 3

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 3 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.9	GERP 0.77, phastCons 1

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

Variant & gene context

Gene: PDSS2
Protein: p.Ser174fs
Coding: c.516_519dup
MANE Select: NM_020381
Type: Duplication
Location: chr6:107274139 (GRCh38)
Gene constraint: LOEUF 0.818 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.28

Full PDSS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

coenzyme Q10 deficiency, primary, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDSS2 p.Lys44fs Likely pathogenic ★ same condition
PDSS2 p.Tyr62fs Likely pathogenic ★ same condition
PDSS2 p.Arg163His Uncertain significance ★★ ⚠ same condition
PDSS2 p.Arg366Cys Uncertain significance ★★ ⚠ same condition
PDSS2 p.Arg385Thr Uncertain significance ★★ ⚠ same condition
PDSS2 p.Arg397fs Uncertain significance ★★ same condition
PDSS2 p.Asn167Ser Uncertain significance ★★ ⚠ same condition
PDSS2 p.Asn201Ser Uncertain significance ★★ ⚠ 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/pdss2-p-ser174fs (accessed [today's date]).

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