Is PLAA p.Thr151fs (c.451dup) pathogenic?

PLAA p.Thr151fs (c.451dup) is classified Uncertain significance in PLAA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). Very rare (popmax 0.00167%, amr).

How common is PLAA p.Thr151fs (c.451dup) in the general population?

PLAA p.Thr151fs (c.451dup) is very rare (popmax 0.00167%, amr) (gnomAD).

PLAA p.Thr151fs

c.451dup · rs2131397259 · VCV1509991

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 10	GERP 0.96, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,016 alleles

Overall 6.84e-05% 1/1,461,842 alleles · very rare

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.Thr151fs
Coding: c.451dup
MANE Select: NM_001031689
dbSNP: rs2131397259
Type: Duplication
Location: chr9:26928213 (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

Similar variants

PLAA p.Thr151Lys Uncertain significance ★ ⚠ same residue
PLAA c.1039+2dup Uncertain significance ★ same type
PLAA p.Lys578fs Uncertain significance ★ same type
PLAA p.Lys722fs Uncertain significance ★ same type
PLAA c.1417+8dup Likely benign ★ same type
PLAA c.1823-10_1823-6dup Likely benign ★ same type
PLAA c.1823-6dup Benign ★ same type
PLAA c.445-17dup Likely benign ★ 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/plaa-p-thr151fs (accessed [today's date]).

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