Is PDSS2 p.Ile334= (c.1002C>T) pathogenic?

PDSS2 p.Ile334= (c.1002C>T) is classified Likely benign in PDSS2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-26). Very rare (popmax 0.00613%, nfe); Associated with coenzyme Q10 deficiency, primary, 3.

What condition is associated with PDSS2 p.Ile334= (c.1002C>T)?

PDSS2 p.Ile334= (c.1002C>T) is associated with coenzyme Q10 deficiency, primary, 3 (ClinVar).

How common is PDSS2 p.Ile334= (c.1002C>T) in the general population?

PDSS2 p.Ile334= (c.1002C>T) is very rare (popmax 0.00613%, nfe) (gnomAD).

PDSS2 p.Ile334=

c.1002C>T · rs375546963 · VCV740822

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00613%, nfe)

Conditions

coenzyme Q10 deficiency, primary, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -4.1
Overall
CADD	4.509	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00613% European (non-Finnish) · 72/1,174,272 alleles

Filtering AF 0.00497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00457%

Overall 0.00492% 79/1,606,864 alleles · very rare exomes 71/1,454,930 · genomes 8/151,934 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00613%	16,309
Remaining individualsnot grpmax-eligible	0.00482%	20,745
Finnishnot grpmax-eligible	0.00315%	31,769
African / African-American	0.00134%	74,716
South Asian	0.0011%	90,906

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.Ile334=
Coding: c.1002C>T
MANE Select: NM_020381
dbSNP: rs375546963
Type: single nucleotide variant
Location: chr6:107210445 (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-ile334 (accessed [today's date]).

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