Is PDSS2 p.Ser382= (c.1146G>A) pathogenic?

PDSS2 p.Ser382= (c.1146G>A) is classified Conflicting classifications of pathogenicity in PDSS2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-26). Rare (popmax 0.252%, eas); Associated with focal segmental glomerulosclerosis.

What condition is associated with PDSS2 p.Ser382= (c.1146G>A)?

PDSS2 p.Ser382= (c.1146G>A) is associated with focal segmental glomerulosclerosis (ClinVar).

How common is PDSS2 p.Ser382= (c.1146G>A) in the general population?

PDSS2 p.Ser382= (c.1146G>A) is rare (popmax 0.252%, eas) (gnomAD).

PDSS2 p.Ser382=

c.1146G>A · rs192206443 · VCV718615

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.252%, eas)

Conditions

focal segmental glomerulosclerosis

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 -5	GERP -3.4
Overall
CADD	4.222	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.252% East Asian · 113/44,884 alleles

Filtering AF 0.214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.2%

Overall 0.0123% 198/1,614,136 alleles · rare exomes 154/1,461,856 · genomes 44/152,280 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.252%	397
Remaining individualsnot grpmax-eligible	0.0608%	1,645
South Asian	0.0263%	3,795
Admixed American	0.00666%	15,004
African / African-American	0.004%	25,013
European (non-Finnish)	0.00136%	73,750

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.Ser382=
Coding: c.1146G>A
MANE Select: NM_020381
dbSNP: rs192206443
Type: single nucleotide variant
Location: chr6:107154673 (GRCh38)
Gene constraint: LOEUF 0.818 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.28
Residue 382: a UniProt-annotated variant site (in coq10d3)

Full PDSS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

focal segmental glomerulosclerosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDSS2 p.Ser382Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PDSS2 p.Pro11Ser Uncertain significance ★ ⚠ same condition
PDSS2 p.Arg163His Uncertain significance ★★ ⚠ same type
PDSS2 p.Arg366Cys Uncertain significance ★★ ⚠ same type
PDSS2 p.Arg366His Uncertain significance ★★ ⚠ same type
PDSS2 p.Arg385Thr Uncertain significance ★★ ⚠ same type
PDSS2 p.Asn167Ser Uncertain significance ★★ ⚠ same type
PDSS2 p.Asn201Ser Uncertain significance ★★ ⚠ same type

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-ser382 (accessed [today's date]).

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