Is KIF1A p.Pro702= (c.2106C>T) pathogenic?

KIF1A p.Pro702= (c.2106C>T) is classified Likely benign in KIF1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-23). Ultra-rare (popmax 0.0509%, afr); Associated with hereditary spastic paraplegia 30.

What condition is associated with KIF1A p.Pro702= (c.2106C>T)?

KIF1A p.Pro702= (c.2106C>T) is associated with hereditary spastic paraplegia 30, neuropathy, hereditary sensory, type 2C, intellectual disability, autosomal dominant 9 (ClinVar).

How common is KIF1A p.Pro702= (c.2106C>T) in the general population?

KIF1A p.Pro702= (c.2106C>T) is ultra-rare (popmax 0.0509%, afr) (gnomAD).

How is Autosomal spastic paraplegia type 30 inherited?

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

KIF1A p.Pro702=

c.2106C>T · rs372340696 · VCV703579

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0509%, afr)

Conditions

hereditary spastic paraplegia 30

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3
Overall
CADD	0.107	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0509% African / African-American · 38/74,636 alleles

Filtering AF 0.0381% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0337%

Overall 0.00478% 76/1,590,666 alleles · ultra-rare exomes 48/1,438,430 · genomes 28/152,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0509%	1,964
Admixed American	0.027%	3,702
South Asian	0.00675%	14,820
Remaining individualsnot grpmax-eligible	0.00489%	20,465
East Asian	0.00227%	44,124
European (non-Finnish)	0.00103%	96,897

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: KIF1A
Protein: p.Pro702=
Coding: c.2106C>T
MANE Select: NM_001244008
dbSNP: rs372340696
Type: single nucleotide variant
Location: chr2:240762729 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 71.38 · 21 PDB
Residue 702: a UniProt-annotated variant site (in spg30a)

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

Disease context

hereditary spastic paraplegia 30 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuropathy, hereditary sensory, type 2C intellectual disability, autosomal dominant 9

For Autosomal spastic paraplegia type 30 (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult

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-pro702 (accessed [today's date]).

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