Is KIF1B p.Pro962= (c.2886G>A) pathogenic?

KIF1B p.Pro962= (c.2886G>A) is classified Likely benign in KIF1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-27). Ultra-rare (popmax 0.0164%, mid); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with KIF1B p.Pro962= (c.2886G>A)?

KIF1B p.Pro962= (c.2886G>A) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is KIF1B p.Pro962= (c.2886G>A) in the general population?

KIF1B p.Pro962= (c.2886G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

KIF1B p.Pro962=

c.2886G>A · rs763515223 · VCV1604620

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 0.14	GERP 0.6, phastCons 0.65
Overall
CADD	12.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000743% 12/1,614,090 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00439%	22,773
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000508%	196,675

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.Pro962=
Coding: c.2886G>A
MANE Select: NM_001365951
dbSNP: rs763515223
Type: single nucleotide variant
Location: chr1:10326321 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.64 · 1 PDB

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.Pro962Leu Uncertain significance ★★ ⚠ same residue
KIF1B p.Pro962Gln 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

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-pro962 (accessed [today's date]).

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