Is PDSS2 p.Lys44fs (c.129dup) pathogenic?

PDSS2 p.Lys44fs (c.129dup) is classified Likely pathogenic in PDSS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-22). Very rare (popmax 8.47e-05%, nfe); Associated with coenzyme Q10 deficiency, primary, 3.

What condition is associated with PDSS2 p.Lys44fs (c.129dup)?

PDSS2 p.Lys44fs (c.129dup) is associated with coenzyme Q10 deficiency, primary, 3 (ClinVar).

How common is PDSS2 p.Lys44fs (c.129dup) in the general population?

PDSS2 p.Lys44fs (c.129dup) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

PDSS2 p.Lys44fs

c.129dup · rs1782160930 · VCV3592878

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 1 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP 0.25, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,010 alleles

Overall 0.000137% 2/1,461,864 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)grpmax	8.47e-05%	1,180,011

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PDSS2
Protein: p.Lys44fs
Coding: c.129dup
MANE Select: NM_020381
dbSNP: rs1782160930
Type: Duplication
Location: chr6:107459156 (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.Tyr62fs Likely pathogenic ★ same condition
PDSS2 p.Ser174fs Uncertain significance ★ 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-lys44fs (accessed [today's date]).

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