Is KIF1A p.Ser1024= (c.3072C>T) pathogenic?

KIF1A p.Ser1024= (c.3072C>T) is classified Benign in KIF1A (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-03). Common (popmax 7.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with neuropathy, hereditary sensory, type 2C.

What condition is associated with KIF1A p.Ser1024= (c.3072C>T)?

KIF1A p.Ser1024= (c.3072C>T) is associated with neuropathy, hereditary sensory, type 2C, hereditary spastic paraplegia 30, intellectual disability, autosomal dominant 9 (ClinVar).

KIF1A p.Ser1024=

Q: How common is KIF1A p.Ser1024= (c.3072C>T) in the general population?

KIF1A p.Ser1024= (c.3072C>T) is common (popmax 7.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.3072C>T · rs73102625 · VCV129389

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 7.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

neuropathy, hereditary sensory, type 2C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.055	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.5	GERP -2.7
Overall
CADD	1.169	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.5% African / African-American · 5,527/73,710 alleles

Filtering AF 7.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.27%

Overall 5.63% 87,914/1,562,738 alleles · common exomes 79,004/1,410,488 · genomes 8,910/152,250 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	10.4%	10
African / African-Americangrpmax	7.5%	13
European (non-Finnish)	6.01%	17
Ashkenazi Jewishnot grpmax-eligible	5.64%	18
Remaining individualsnot grpmax-eligible	5.54%	18
Middle Eastern	5%	20
Finnishnot grpmax-eligible	4.89%	20
South Asian	3.35%	30
Admixed American	3.26%	31
East Asian	0.445%	225

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser1024=
Coding: c.3072C>T
MANE Select: NM_001244008
dbSNP: rs73102625
Type: single nucleotide variant
Location: chr2:240746169 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 71.38 · 21 PDB
Residue 1024: 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 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-ser1024 (accessed [today's date]).

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