Is PLAA p.Glu350Val (c.1049A>T) pathogenic?

PLAA p.Glu350Val (c.1049A>T) is classified Pathogenic in PLAA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-08-07). AlphaMissense: likely pathogenic (0.6978); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies.

How common is PLAA p.Glu350Val (c.1049A>T) in the general population?

PLAA p.Glu350Val (c.1049A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLAA p.Glu350Val (c.1049A>T)?

AlphaMissense predicts likely pathogenic (score 0.6978) — an in-silico prediction, not a clinical call.

PLAA p.Glu350Val

Q: What condition is associated with PLAA p.Glu350Val (c.1049A>T)?

PLAA p.Glu350Val (c.1049A>T) is associated with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (ClinVar).

c.1049A>T · rs1824723269 · VCV975038

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies

Computational evidence

Protein change
AlphaMissense	0.6978	likely pathogenic ✓ concordant with ClinVar
REVEL	0.46	indeterminate
SaProt	LLR -7.73	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.34	acceptor loss · deltas
Pangolin	Δ0.39	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.094 · regional, not allelic
Overall
CADD	26.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PLAA
Protein: p.Glu350Val
Coding: c.1049A>T
MANE Select: NM_001031689
dbSNP: rs1824723269
Type: single nucleotide variant
Location: chr9:26920375 (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.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.Thr114Ala Uncertain significance ★★ ⚠ same condition
PLAA p.Thr304Arg Uncertain significance ★★ ⚠ same condition
PLAA p.Tyr775His 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-glu350val (accessed [today's date]).

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