Is KIF1A p.Pro43= (c.129C>G) pathogenic?

KIF1A p.Pro43= (c.129C>G) is classified Likely benign in KIF1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-09). Absent from gnomAD v4.1; Associated with neuropathy, hereditary sensory, type 2C.

What condition is associated with KIF1A p.Pro43= (c.129C>G)?

KIF1A p.Pro43= (c.129C>G) is associated with neuropathy, hereditary sensory, type 2C, hereditary spastic paraplegia 30, intellectual disability, autosomal dominant 9 (ClinVar).

How common is KIF1A p.Pro43= (c.129C>G) in the general population?

KIF1A p.Pro43= (c.129C>G) is absent from gnomAD v4.1 (gnomAD).

KIF1A p.Pro43=

Q: How is Hereditary sensory and autonomic neuropathy type 2 inherited?

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

c.129C>G · VCV3757713

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neuropathy, hereditary sensory, type 2C

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 1.7	GERP -4.7, phastCons 1
Overall
CADD	11.19	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: KIF1A
Protein: p.Pro43=
Coding: c.129C>G
MANE Select: NM_001244008
Type: single nucleotide variant
Location: chr2:240789290 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 71.38 · 21 PDB
Residue 43: the kinesin motor domain; a turn

Full KIF1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuropathy, hereditary sensory, type 2C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia 30 intellectual disability, autosomal dominant 9

For Hereditary sensory and autonomic neuropathy type 2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

KIF1A c.2582+1G>A Pathogenic/Likely pathogenic ★★ same condition
KIF1A c.798+1G>A Pathogenic/Likely pathogenic ★★ same condition
KIF1A p.Ala255Asp Likely pathogenic ★★ same condition
KIF1A p.Ala85Asp Pathogenic/Likely pathogenic ★★ same condition
KIF1A p.Arg11Gln Pathogenic/Likely pathogenic ★★ same condition
KIF1A p.Arg11Trp Pathogenic/Likely pathogenic ★★ same condition
KIF1A p.Arg13Cys Pathogenic/Likely pathogenic ★★ same condition
KIF1A p.Arg13His Pathogenic/Likely 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/kif1a-p-pro43 (accessed [today's date]).

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