Is KIF1B p.Phe303= (c.909T>C) pathogenic?

KIF1B p.Phe303= (c.909T>C) is classified Likely benign in KIF1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-06). Very rare (popmax 0.000173%, nfe); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with KIF1B p.Phe303= (c.909T>C)?

KIF1B p.Phe303= (c.909T>C) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is KIF1B p.Phe303= (c.909T>C) in the general population?

KIF1B p.Phe303= (c.909T>C) is very rare (popmax 0.000173%, nfe) (gnomAD).

KIF1B p.Phe303=

c.909T>C · rs1362385553 · VCV1765124

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000173%, nfe)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.71, phastCons 1
Overall
CADD	11.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000173% European (non-Finnish) · 2/1,157,270 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000126% 2/1,588,782 alleles · very rare exomes 2/1,436,438 · genomes 0/152,344 · 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: KIF1B
Protein: p.Phe303=
Coding: c.909T>C
MANE Select: NM_001365951
dbSNP: rs1362385553
Type: single nucleotide variant
Location: chr1:10275454 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.64 · 1 PDB
Residue 303: the kinesin motor domain; the 'interaction with kifbp' region

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 p.Phe303Cys Uncertain significance ★ ⚠ same residue
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

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-phe303 (accessed [today's date]).

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