Is KIF1B p.Glu1663Gly (c.4988A>G) pathogenic?

KIF1B p.Glu1663Gly (c.4988A>G) is classified Uncertain significance in KIF1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). AlphaMissense: likely benign (0.178); Absent from gnomAD v4.1.

How common is KIF1B p.Glu1663Gly (c.4988A>G) in the general population?

KIF1B p.Glu1663Gly (c.4988A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIF1B p.Glu1663Gly (c.4988A>G)?

AlphaMissense predicts likely benign (score 0.178) — an in-silico prediction, not a clinical call.

KIF1B p.Glu1663Gly

c.4988A>G · rs1638827878 · VCV1743581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.178 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.178	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 11 kb · p 0.01 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Glu1663Gly
Coding: c.4988A>G
MANE Select: NM_001365951
dbSNP: rs1638827878
Type: single nucleotide variant
Location: chr1:10374357 (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

Similar variants

KIF1B p.Glu1663Ala 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
KIF1B c.2115+6A>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-glu1663gly (accessed [today's date]).

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