Is KIF1C p.Pro600= (c.1800G>A) pathogenic?

KIF1C p.Pro600= (c.1800G>A) is classified Likely benign in KIF1C (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-14). Very rare (popmax 0.00667%, amr); Associated with spastic ataxia 2.

What condition is associated with KIF1C p.Pro600= (c.1800G>A)?

KIF1C p.Pro600= (c.1800G>A) is associated with spastic ataxia 2 (ClinVar).

How common is KIF1C p.Pro600= (c.1800G>A) in the general population?

KIF1C p.Pro600= (c.1800G>A) is very rare (popmax 0.00667%, amr) (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.Pro600=

c.1800G>A · rs200771979 · VCV2140019

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

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 0.21	GERP -0.42, phastCons 0.93
Overall
CADD	17.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,002 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000929% 15/1,614,090 alleles · very rare exomes 12/1,461,854 · genomes 3/152,236 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,001
African / African-American	0.00267%	37,470
East Asian	0.00223%	44,898
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00156%	64,044
European (non-Finnish)	0.000508%	196,673

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.Pro600=
Coding: c.1800G>A
MANE Select: NM_006612
dbSNP: rs200771979
Type: single nucleotide variant
Location: chr17:5020541 (GRCh38)
Gene constraint: LOEUF 0.609 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.43 · 2 PDB

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.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
KIF1C p.Ala1043Val 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-pro600 (accessed [today's date]).

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