Is PLP1 p.Val97= (c.291C>G) pathogenic?

PLP1 p.Val97= (c.291C>G) is classified Likely benign in PLP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). Absent from gnomAD v4.1; Associated with hereditary spastic paraplegia 2.

What condition is associated with PLP1 p.Val97= (c.291C>G)?

PLP1 p.Val97= (c.291C>G) is associated with hereditary spastic paraplegia 2 (ClinVar).

How common is PLP1 p.Val97= (c.291C>G) in the general population?

PLP1 p.Val97= (c.291C>G) is absent from gnomAD v4.1 (gnomAD).

How is Spastic paraplegia type 2 inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PLP1 p.Val97=

c.291C>G · rs2147764368 · VCV1566555

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary spastic paraplegia 2

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 1.5	GERP -0.11, phastCons 1
Overall
CADD	11.34	PHRED · no single calibrated threshold — expert panels disagree

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: PLP1
Protein: p.Val97=
Coding: c.291C>G
MANE Select: NM_000533
dbSNP: rs2147764368
Type: single nucleotide variant
Location: chrX:103786564 (GRCh38)
Structure: AlphaFold pLDDT 77.81 · 1 PDB

Full PLP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spastic paraplegia type 2 (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood

Similar variants

PLP1 c.696+1G>A Pathogenic/Likely pathogenic ★★ same condition
PLP1 p.Gln69Ter Pathogenic ★★ same condition
PLP1 p.Gly246Ala Pathogenic/Likely pathogenic ★★ same condition
PLP1 p.His130Tyr Likely pathogenic ★★ ⚠ same condition
PLP1 p.His148Tyr Pathogenic/Likely pathogenic ★★ ⚠ same condition
PLP1 p.Ile47Thr Likely pathogenic ★★ same condition
PLP1 p.Lys151= Pathogenic/Likely pathogenic ★★ same condition
PLP1 p.Met1Arg Pathogenic ★★ 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/plp1-p-val97 (accessed [today's date]).

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