Is PLAA p.Ser50= (c.150T>C) pathogenic?

PLAA p.Ser50= (c.150T>C) is classified Conflicting classifications of pathogenicity in PLAA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-18). Ultra-rare (popmax 0.0157%, amr); Associated with Inborn genetic diseases.

What condition is associated with PLAA p.Ser50= (c.150T>C)?

PLAA p.Ser50= (c.150T>C) is associated with Inborn genetic diseases (ClinVar).

How common is PLAA p.Ser50= (c.150T>C) in the general population?

PLAA p.Ser50= (c.150T>C) is ultra-rare (popmax 0.0157%, amr) (gnomAD).

PLAA p.Ser50=

c.150T>C · rs756103623 · VCV1365478

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, amr)

Conditions

Inborn genetic diseases

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 6.8	GERP 0.63, phastCons 1
Overall
CADD	14.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0157% Admixed American · 7/44,584 alleles

Filtering AF 0.0073% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00517%

Overall 0.00298% 46/1,544,844 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0157%	6,369
Remaining individualsnot grpmax-eligible	0.00671%	14,901
European (non-Finnish)	0.00304%	32,914

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: PLAA
Protein: p.Ser50=
Coding: c.150T>C
MANE Select: NM_001031689
dbSNP: rs756103623
Type: single nucleotide variant
Location: chr9:26935206 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB
Residue 50: a modified residue (phosphoserine)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLAA p.Ser50Arg Uncertain significance ★ ⚠ same residue
PLAA p.Ala271Val Uncertain significance ★★ ⚠ same condition
PLAA p.Arg268Gln Uncertain significance ★★ ⚠ same condition
PLAA p.Arg373Thr Uncertain significance ★★ ⚠ same condition
PLAA p.Arg499Cys Uncertain significance ★★ same condition
PLAA p.Arg7Ser Uncertain significance ★★ ⚠ same condition
PLAA p.Asn410Ser Uncertain significance ★★ ⚠ same condition
PLAA p.Asn520Ser 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/plaa-p-ser50 (accessed [today's date]).

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