Is PDSS2 p.Ser26Ala (c.76T>G) pathogenic?

PDSS2 p.Ser26Ala (c.76T>G) is classified Uncertain significance in PDSS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0759); Absent from gnomAD v4.1; Associated with coenzyme Q10 deficiency, primary, 3.

What condition is associated with PDSS2 p.Ser26Ala (c.76T>G)?

PDSS2 p.Ser26Ala (c.76T>G) is associated with coenzyme Q10 deficiency, primary, 3 (ClinVar).

How common is PDSS2 p.Ser26Ala (c.76T>G) in the general population?

PDSS2 p.Ser26Ala (c.76T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDSS2 p.Ser26Ala (c.76T>G)?

AlphaMissense predicts likely benign (score 0.0759) — an in-silico prediction, not a clinical call.

PDSS2 p.Ser26Ala

c.76T>G · rs1356132916 · VCV1902462

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0759 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

coenzyme Q10 deficiency, primary, 3

Computational evidence

Protein change
AlphaMissense	0.0759	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -7.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -0.14, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 305 kb · p 0.17 · regional, not allelic
Overall
CADD	17.14	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PDSS2
Protein: p.Ser26Ala
Coding: c.76T>G
MANE Select: NM_020381
dbSNP: rs1356132916
Type: single nucleotide variant
Location: chr6:107459210 (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.Ser26Phe Likely benign ★ same residue
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

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-ser26ala (accessed [today's date]).

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