Is PLAA p.Pro81Ter (c.240_241insTAG) pathogenic?

PLAA p.Pro81Ter (c.240241insTAG) is classified Pathogenic in PLAA (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-30). Absent from gnomAD; Associated with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies.

How common is PLAA p.Pro81Ter (c.240_241insTAG) in the general population?

PLAA p.Pro81Ter (c.240_241insTAG) is absent from gnomAD (gnomAD).

PLAA p.Pro81Ter

Q: What condition is associated with PLAA p.Pro81Ter (c.240_241insTAG)?

PLAA p.Pro81Ter (c.240_241insTAG) is associated with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (ClinVar).

c.240_241insTAG · rs1587185107 · VCV807466

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 1.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PLAA
Protein: p.Pro81Ter
Coding: c.240_241insTAG
MANE Select: NM_001031689
dbSNP: rs1587185107
Type: Insertion
Location: chr9:26935115 (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

neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLAA p.Pro81Arg Uncertain significance ★★ ⚠ same residue
PLAA p.Arg524Ter Likely pathogenic ★★ same condition
PLAA p.Ala264Thr Uncertain significance ★★ ⚠ same condition
PLAA p.Gly457Ala Uncertain significance ★★ ⚠ same condition
PLAA p.Ile356Met Uncertain significance ★★ same condition
PLAA p.Pro161Ser Uncertain significance ★★ ⚠ same condition
PLAA p.Pro653Ile Uncertain significance ★★ same condition
PLAA p.Thr114Ala 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-pro81ter (accessed [today's date]).

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