Is KIF1A p.Phe86= (c.258T>C) pathogenic?

KIF1A p.Phe86= (c.258T>C) is classified Conflicting classifications of pathogenicity in KIF1A (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-02-02). Rare (popmax 0.653%, eas); Associated with neuropathy, hereditary sensory, type 2C.

What condition is associated with KIF1A p.Phe86= (c.258T>C)?

KIF1A p.Phe86= (c.258T>C) is associated with neuropathy, hereditary sensory, type 2C, hereditary spastic paraplegia 30, intellectual disability, autosomal dominant 9 (ClinVar).

How common is KIF1A p.Phe86= (c.258T>C) in the general population?

KIF1A p.Phe86= (c.258T>C) is rare (popmax 0.653%, eas) (gnomAD).

KIF1A p.Phe86=

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.258T>C · rs183284555 · VCV382122

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.653%, eas)

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 -3.8	GERP -5.4
Overall
CADD	5.255	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.653% East Asian · 293/44,844 alleles

Filtering AF 0.592% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.568%

Overall 0.0231% 373/1,613,538 alleles · rare exomes 340/1,461,432 · genomes 33/152,106 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.653%	153
South Asian	0.033%	3,034
Remaining individualsnot grpmax-eligible	0.0272%	3,675
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
European (non-Finnish)	0.00263%	38,058
Admixed American	0.00167%	59,980

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.Phe86=
Coding: c.258T>C
MANE Select: NM_001244008
dbSNP: rs183284555
Type: single nucleotide variant
Location: chr2:240788156 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 71.38 · 21 PDB
Residue 86: the kinesin motor domain; an α-helix

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-phe86 (accessed [today's date]).

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