Is PDSS2 p.Val116= (c.348G>T) pathogenic?

PDSS2 p.Val116= (c.348G>T) is classified Likely benign in PDSS2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-10). Very rare (popmax 0.00667%, amr); Associated with coenzyme Q10 deficiency, primary, 3.

What condition is associated with PDSS2 p.Val116= (c.348G>T)?

PDSS2 p.Val116= (c.348G>T) is associated with coenzyme Q10 deficiency, primary, 3 (ClinVar).

How common is PDSS2 p.Val116= (c.348G>T) in the general population?

PDSS2 p.Val116= (c.348G>T) is very rare (popmax 0.00667%, amr) (gnomAD).

PDSS2 p.Val116=

c.348G>T · rs779485875 · VCV261252

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.8	GERP -2.9
Overall
CADD	5.793	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,008 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00031% 5/1,613,380 alleles · very rare exomes 5/1,461,230 · genomes 0/152,150 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,002
European (non-Finnish)	8.48e-05%	1,179,491

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.Val116=
Coding: c.348G>T
MANE Select: NM_020381
dbSNP: rs779485875
Type: single nucleotide variant
Location: chr6:107334281 (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-val116 (accessed [today's date]).

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