Is KIF1B p.Ser2= (c.6G>A) pathogenic?

KIF1B p.Ser2= (c.6G>A) is classified Likely benign in KIF1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-19). Very rare (popmax 0.00134%, afr); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with KIF1B p.Ser2= (c.6G>A)?

KIF1B p.Ser2= (c.6G>A) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is KIF1B p.Ser2= (c.6G>A) in the general population?

KIF1B p.Ser2= (c.6G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

KIF1B p.Ser2=

c.6G>A · rs1646993926 · VCV1756609

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 0.27	GERP -4.2, phastCons 0.93
Overall
CADD	11.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,754 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000621% 10/1,610,534 alleles · very rare exomes 9/1,458,652 · genomes 1/151,882 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,754
South Asian	0.0011%	90,896
European (non-Finnish)	0.00068%	147,161

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.Ser2=
Coding: c.6G>A
MANE Select: NM_001365951
dbSNP: rs1646993926
Type: single nucleotide variant
Location: chr1:10232334 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.64 · 1 PDB
Residue 2: a modified residue (n-acetylserine)

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.Ser2Leu 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-ser2 (accessed [today's date]).

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