Is KIF5C p.Ser89Pro (c.265T>C) pathogenic?

KIF5C p.Ser89Pro (c.265T>C) is classified Pathogenic in KIF5C (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9986); Absent from gnomAD v4.1; Associated with complex cortical dysplasia with other brain malformations 2.

What condition is associated with KIF5C p.Ser89Pro (c.265T>C)?

KIF5C p.Ser89Pro (c.265T>C) is associated with complex cortical dysplasia with other brain malformations 2 (ClinVar).

How common is KIF5C p.Ser89Pro (c.265T>C) in the general population?

KIF5C p.Ser89Pro (c.265T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIF5C p.Ser89Pro (c.265T>C)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

KIF5C p.Ser89Pro

c.265T>C · rs1215264639 · VCV1878628

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

complex cortical dysplasia with other brain malformations 2

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic ✓ concordant with ClinVar · top 6% in KIF5C
REVEL	0.734	pathogenic-leaning
SaProt	LLR -13.29	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.9, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 86 kb · p 7.3e-29 · regional, not allelic
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

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: KIF5C
Protein: p.Ser89Pro
Coding: c.265T>C
MANE Select: NM_004522
dbSNP: rs1215264639
Type: single nucleotide variant
Location: chr2:148929328 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.70
Residue 89: the kinesin motor domain; a binding site

Full KIF5C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

complex cortical dysplasia with other brain malformations 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KIF5C p.Glu237Lys Pathogenic/Likely pathogenic ★★ same condition
KIF5C p.Lys92Arg Likely pathogenic ★★ same condition
KIF5C p.Thr93Ile Pathogenic/Likely pathogenic ★★ same condition
KIF5C p.Tyr135Cys Likely pathogenic ★★ same condition
KIF5C p.Arg286Trp Uncertain significance ★★ ⚠ same condition
KIF5C p.Met891Thr Uncertain significance ★★ same condition
KIF5C p.Thr396Asn Uncertain significance ★★ ⚠ same condition
KIF5C p.Ala268Ser Likely benign ★★ 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/kif5c-p-ser89pro (accessed [today's date]).

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