Is KIF1B p.Val593= (c.1779T>G) pathogenic?

KIF1B p.Val593= (c.1779T>G) is classified Likely benign in KIF1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). Very rare (popmax 8.48e-05%, nfe).

How common is KIF1B p.Val593= (c.1779T>G) in the general population?

KIF1B p.Val593= (c.1779T>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

KIF1B p.Val593=

c.1779T>G · VCV3864024

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)

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 0.043	GERP 1.3, phastCons 0.97
Overall
CADD	11.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,218 alleles

Overall 6.2e-05% 1/1,613,166 alleles · very rare exomes 1/1,460,906 · genomes 0/152,260 · 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.Val593=
Coding: c.1779T>G
MANE Select: NM_001365951
Type: single nucleotide variant
Location: chr1:10296583 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.64 · 1 PDB
Residue 593: the fha domain; a β-strand

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

Similar variants

KIF1B p.Val593Asp Uncertain significance ★★ ⚠ same residue
KIF1B p.Val593Leu Uncertain significance ★ ⚠ same residue
KIF1B c.1434+5G>A Uncertain significance ★★ same type
KIF1B c.1590+5G>A Uncertain significance ★★ same type
KIF1B c.1671-3C>A Uncertain significance ★★ same type
KIF1B c.1671-3C>G Uncertain significance ★★ same type
KIF1B c.1861+3G>A Uncertain significance ★★ same type
KIF1B c.2115+6205C>T Uncertain significance ★★ same type

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-val593 (accessed [today's date]).

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