Is KIF1A p.Ser1007= (c.3021G>A) pathogenic?

KIF1A p.Ser1007= (c.3021G>A) is classified Likely benign in KIF1A (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-01). Ultra-rare (popmax 0.0286%, sas); Associated with neuropathy, hereditary sensory, type 2C.

What condition is associated with KIF1A p.Ser1007= (c.3021G>A)?

KIF1A p.Ser1007= (c.3021G>A) is associated with neuropathy, hereditary sensory, type 2C, hereditary spastic paraplegia 30, intellectual disability, autosomal dominant 9 (ClinVar).

How common is KIF1A p.Ser1007= (c.3021G>A) in the general population?

KIF1A p.Ser1007= (c.3021G>A) is ultra-rare (popmax 0.0286%, sas) (gnomAD).

KIF1A p.Ser1007=

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.3021G>A · rs769618125 · VCV641030

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0286%, sas)

Conditions

neuropathy, hereditary sensory, type 2C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.128	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.7
Overall
CADD	3.603	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0286% South Asian · 26/91,046 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00267% 43/1,613,320 alleles · ultra-rare exomes 39/1,461,186 · genomes 4/152,134 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0286%	3,502
East Asian	0.0134%	7,481
Remaining individualsnot grpmax-eligible	0.0016%	62,432
Finnishnot grpmax-eligible	0.00157%	63,876
African / African-American	0.00134%	74,886
European (non-Finnish)	0.000678%	147,456

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.Ser1007=
Coding: c.3021G>A
MANE Select: NM_001244008
dbSNP: rs769618125
Type: single nucleotide variant
Location: chr2:240747278 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 71.38 · 21 PDB
Residue 1007: a UniProt-annotated variant site (in spg30a)

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 p.Ser1007Leu Uncertain significance ★ ⚠ same residue
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

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-ser1007 (accessed [today's date]).

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