Is PDSS2 p.Lys347= (c.1041G>A) pathogenic?

PDSS2 p.Lys347= (c.1041G>A) is classified Uncertain significance in PDSS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-29). Very rare (popmax 0.00815%, afr); Associated with coenzyme Q10 deficiency, primary, 3.

What condition is associated with PDSS2 p.Lys347= (c.1041G>A)?

PDSS2 p.Lys347= (c.1041G>A) is associated with coenzyme Q10 deficiency, primary, 3 (ClinVar).

How common is PDSS2 p.Lys347= (c.1041G>A) in the general population?

PDSS2 p.Lys347= (c.1041G>A) is very rare (popmax 0.00815%, afr) (gnomAD).

PDSS2 p.Lys347=

c.1041G>A · VCV3592862

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00815%, afr)

Conditions

coenzyme Q10 deficiency, primary, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.73	acceptor loss, 32 bp away · masked 0 · deltas
Pangolin	Δ0.29	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.3	GERP 1.7, phastCons 1
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00815% African / African-American · 6/73,646 alleles

Filtering AF 0.00352% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000387% 6/1,549,208 alleles · very rare exomes 3/1,397,106 · genomes 3/152,102 · joint denominator

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.Lys347=
Coding: c.1041G>A
MANE Select: NM_020381
Type: single nucleotide variant
Location: chr6:107193822 (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.Arg163His Uncertain significance ★★ ⚠ same condition
PDSS2 p.Arg366Cys Uncertain significance ★★ ⚠ same condition
PDSS2 p.Arg385Thr Uncertain significance ★★ ⚠ same condition
PDSS2 p.Asn167Ser Uncertain significance ★★ ⚠ same condition
PDSS2 p.Asn201Ser Uncertain significance ★★ ⚠ same condition
PDSS2 p.Asn390Ser Uncertain significance ★★ ⚠ same condition
PDSS2 p.Asp180His Uncertain significance ★★ same condition
PDSS2 p.Gly176Arg 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-lys347 (accessed [today's date]).

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