Is KIF1A p.Val73= (c.219G>A) pathogenic?

KIF1A p.Val73= (c.219G>A) is classified Likely benign in KIF1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-20). Very rare (popmax 8.48e-05%, nfe); Associated with neuropathy, hereditary sensory, type 2C.

What condition is associated with KIF1A p.Val73= (c.219G>A)?

KIF1A p.Val73= (c.219G>A) is associated with neuropathy, hereditary sensory, type 2C, hereditary spastic paraplegia 30, intellectual disability, autosomal dominant 9 (ClinVar).

How common is KIF1A p.Val73= (c.219G>A) in the general population?

KIF1A p.Val73= (c.219G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

KIF1A p.Val73=

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.219G>A · VCV4789407

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

neuropathy, hereditary sensory, type 2C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	donor gain · deltas
Constraint at this position
Conservation	phyloP -1.1	GERP -3.6, phastCons 0.001
Overall
CADD	14.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,878 alleles

Overall 6.2e-05% 1/1,613,888 alleles · very rare exomes 1/1,461,554 · genomes 0/152,334 · joint denominator

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.Val73=
Coding: c.219G>A
MANE Select: NM_001244008
Type: single nucleotide variant
Location: chr2:240788195 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 71.38 · 21 PDB
Residue 73: 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 p.Val73Ala Uncertain significance ★ ⚠ same residue
KIF1A p.Val73Leu Conflicting classifications of pathogenicity ★ ⚠ 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

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-val73 (accessed [today's date]).

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