Is KIF1A p.Pro501= (c.1503A>G) pathogenic?

KIF1A p.Pro501= (c.1503A>G) is classified Benign/Likely benign in KIF1A (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.04%, sas); Associated with neuropathy, hereditary sensory, type 2C.

What condition is associated with KIF1A p.Pro501= (c.1503A>G)?

KIF1A p.Pro501= (c.1503A>G) is associated with neuropathy, hereditary sensory, type 2C, hereditary spastic paraplegia 30, intellectual disability, autosomal dominant 9 (ClinVar).

How common is KIF1A p.Pro501= (c.1503A>G) in the general population?

KIF1A p.Pro501= (c.1503A>G) is low-frequency (popmax 3.04%, sas) (gnomAD).

KIF1A p.Pro501=

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.1503A>G · rs35663732 · VCV129384

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.04%, sas)

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 -12	GERP -3.7
Overall
CADD	0.085	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.04% South Asian · 2,764/90,978 alleles

Filtering AF 2.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.91%

Overall 1.87% 30,203/1,612,896 alleles · low-frequency exomes 27,462/1,460,706 · genomes 2,741/152,190 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	3.04%	33
Finnishnot grpmax-eligible	2.55%	39
Ashkenazi Jewishnot grpmax-eligible	2.14%	47
Remaining individualsnot grpmax-eligible	2.06%	48
European (non-Finnish)	1.88%	53
Middle Eastern	1.47%	68
Admixed American	1.3%	77
African / African-American	0.94%	106
Amishnot grpmax-eligible	0.768%	130
East Asian	0.428%	234

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.Pro501=
Coding: c.1503A>G
MANE Select: NM_001244008
dbSNP: rs35663732
Type: single nucleotide variant
Location: chr2:240767340 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 71.38 · 21 PDB

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 hereditary spastic paraplegia

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-pro501 (accessed [today's date]).

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