Is NIPA1 p.Pro159= (c.477A>G) pathogenic?

NIPA1 p.Pro159= (c.477A>G) is classified Uncertain significance in NIPA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-15). Absent from gnomAD v4.1; Associated with hereditary spastic paraplegia 6.

What condition is associated with NIPA1 p.Pro159= (c.477A>G)?

NIPA1 p.Pro159= (c.477A>G) is associated with hereditary spastic paraplegia 6 (ClinVar).

How common is NIPA1 p.Pro159= (c.477A>G) in the general population?

NIPA1 p.Pro159= (c.477A>G) is absent from gnomAD v4.1 (gnomAD).

How is Autosomal dominant spastic paraplegia type 6 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

NIPA1 p.Pro159=

c.477A>G · rs2140875018 · VCV1375588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary spastic paraplegia 6

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 9	GERP 2.1, phastCons 1
Overall
CADD	16.01	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: NIPA1
Protein: p.Pro159=
Coding: c.477A>G
MANE Select: NM_144599
dbSNP: rs2140875018
Type: single nucleotide variant
Location: chr15:22820472 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI 0.27 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 86.00

Full NIPA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant spastic paraplegia type 6 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

NIPA1 p.Gly106Arg Pathogenic ★★ same condition
NIPA1 c.*548A>C Uncertain significance ★★ same condition
NIPA1 p.Ala100Val Uncertain significance ★★ ⚠ same condition
NIPA1 p.Arg281Trp Uncertain significance ★★ same condition
NIPA1 p.Ile188Val Uncertain significance ★★ ⚠ same condition
NIPA1 p.Ile74Met Uncertain significance ★★ ⚠ same condition
NIPA1 p.Ile81Thr Uncertain significance ★★ ⚠ same condition
NIPA1 p.Leu98Met 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/nipa1-p-pro159 (accessed [today's date]).

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