Is KIF1B p.Val91= (c.273C>T) pathogenic?

KIF1B p.Val91= (c.273C>T) is classified Likely benign in KIF1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-13). Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with KIF1B p.Val91= (c.273C>T)?

KIF1B p.Val91= (c.273C>T) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is KIF1B p.Val91= (c.273C>T) in the general population?

KIF1B p.Val91= (c.273C>T) is absent from gnomAD v4.1 (gnomAD).

KIF1B p.Val91=

c.273C>T · VCV3288462

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.66 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.54	GERP -0.81, phastCons 0.025
Overall
CADD	8.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KIF1B
Protein: p.Val91=
Coding: c.273C>T
MANE Select: NM_001365951
Type: single nucleotide variant
Location: chr1:10258582 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.64 · 1 PDB
Residue 91: the kinesin motor domain

Full KIF1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KIF1B c.1590+5G>A Uncertain significance ★★ same condition
KIF1B c.1671-3C>A Uncertain significance ★★ same condition
KIF1B c.1671-3C>G Uncertain significance ★★ same condition
KIF1B c.1861+3G>A Uncertain significance ★★ same condition
KIF1B c.2115+6A>T Uncertain significance ★★ same condition
KIF1B c.2358+1G>A Uncertain significance ★★ same condition
KIF1B c.2676-3T>C Uncertain significance ★★ same condition
KIF1B c.2924+5G>A Uncertain significance ★★ 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/kif1b-p-val91 (accessed [today's date]).

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