Is PLAA p.Ser482Leu (c.1445C>T) pathogenic?

PLAA p.Ser482Leu (c.1445C>T) is classified Conflicting classifications of pathogenicity in PLAA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-12-28). AlphaMissense: likely benign (0.078); Rare (popmax 0.429%, mid); Associated with Inborn genetic diseases.

What condition is associated with PLAA p.Ser482Leu (c.1445C>T)?

PLAA p.Ser482Leu (c.1445C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PLAA p.Ser482Leu (c.1445C>T) in the general population?

PLAA p.Ser482Leu (c.1445C>T) is rare (popmax 0.429%, mid) (gnomAD).

What do computational predictors say about PLAA p.Ser482Leu (c.1445C>T)?

AlphaMissense predicts likely benign (score 0.078) — an in-silico prediction, not a clinical call.

PLAA p.Ser482Leu

c.1445C>T · rs140970730 · VCV1345698

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.078 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.429%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.078	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -8.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.31	donor loss · deltas
Pangolin	Δ0.21	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.094 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.429% Middle Eastern · 26/6,058 alleles

Filtering AF 0.301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.258%

Overall 0.0767% 1,238/1,613,864 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.429%	233
Admixed American	0.147%	682
Remaining individualsnot grpmax-eligible	0.0944%	1,059
European (non-Finnish)	0.0859%	1,164
Finnishnot grpmax-eligible	0.0422%	2,370
South Asian	0.0143%	7,006
African / African-American	0.0133%	7,503
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,586

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.Ser482Leu
Coding: c.1445C>T
MANE Select: NM_001031689
dbSNP: rs140970730
Type: single nucleotide variant
Location: chr9:26917138 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB

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.Ser482= Likely benign ★ 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-ser482leu (accessed [today's date]).

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