Is KIF1C p.Pro1069= (c.3207A>C) pathogenic?

KIF1C p.Pro1069= (c.3207A>C) is classified Likely benign in KIF1C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). Very rare (popmax 0.00413%, afr); Associated with spastic ataxia 2.

What condition is associated with KIF1C p.Pro1069= (c.3207A>C)?

KIF1C p.Pro1069= (c.3207A>C) is associated with spastic ataxia 2 (ClinVar).

How common is KIF1C p.Pro1069= (c.3207A>C) in the general population?

KIF1C p.Pro1069= (c.3207A>C) is very rare (popmax 0.00413%, afr) (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.Pro1069=

c.3207A>C · rs768877923 · VCV719857

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00413%, afr)

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 0.053	GERP -2.8, phastCons 0.007
Overall
CADD	3.387	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00413% African / African-American · 3/72,698 alleles

Filtering AF 0.0011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000504%

Overall 0.00102% 16/1,573,386 alleles · very rare exomes 10/1,422,356 · genomes 6/151,030 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00413%	24,233
Remaining individualsnot grpmax-eligible	0.00165%	60,616
European (non-Finnish)	0.00104%	96,614

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.Pro1069=
Coding: c.3207A>C
MANE Select: NM_006612
dbSNP: rs768877923
Type: single nucleotide variant
Location: chr17:5024046 (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 1069: 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.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-pro1069 (accessed [today's date]).

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