Is KIF1C p.Pro413= (c.1239C>G) pathogenic?

KIF1C p.Pro413= (c.1239C>G) is classified Likely benign in KIF1C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). Very rare (popmax 0.00017%, nfe); Associated with spastic ataxia 2.

What condition is associated with KIF1C p.Pro413= (c.1239C>G)?

KIF1C p.Pro413= (c.1239C>G) is associated with spastic ataxia 2 (ClinVar).

How common is KIF1C p.Pro413= (c.1239C>G) in the general population?

KIF1C p.Pro413= (c.1239C>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Autosomal spastic paraplegia type 58 inherited?

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

KIF1C p.Pro413=

c.1239C>G · rs2143331394 · VCV1606142

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

spastic ataxia 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 0.27	GERP -3.1, phastCons 0.97
Overall
CADD	2.259	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,416 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,611,866 alleles · very rare exomes 2/1,459,606 · genomes 0/152,260 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: KIF1C
Protein: p.Pro413=
Coding: c.1239C>G
MANE Select: NM_006612
dbSNP: rs2143331394
Type: single nucleotide variant
Location: chr17:5006988 (GRCh38)
Gene constraint: LOEUF 0.609 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.43 · 2 PDB
Residue 413: the 'disordered' region

Full KIF1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Autosomal spastic paraplegia type 58 (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood, Elderly, Infancy

Similar variants

KIF1C p.Pro413Leu Uncertain significance ★ ⚠ same residue
KIF1C p.Arg216Cys Likely pathogenic ★★ same condition
KIF1C p.Arg669Ter Pathogenic/Likely pathogenic ★★ same condition
KIF1C p.Arg731Ter Pathogenic ★★ same condition
KIF1C p.Pro176Leu Pathogenic/Likely pathogenic ★★ same condition
KIF1C c.1415+8G>T Uncertain significance ★★ same condition
KIF1C c.1937+5G>A Uncertain significance ★★ same condition
KIF1C c.363+5G>A 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/kif1c-p-pro413 (accessed [today's date]).

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