Is KIF2A p.Pro152Ser (c.454C>T) pathogenic?

KIF2A p.Pro152Ser (c.454C>T) is classified Uncertain significance in KIF2A (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.0806); Very rare (popmax 0.0011%, sas); Associated with complex cortical dysplasia with other brain malformations 3.

What condition is associated with KIF2A p.Pro152Ser (c.454C>T)?

KIF2A p.Pro152Ser (c.454C>T) is associated with complex cortical dysplasia with other brain malformations 3 (ClinVar).

How common is KIF2A p.Pro152Ser (c.454C>T) in the general population?

KIF2A p.Pro152Ser (c.454C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about KIF2A p.Pro152Ser (c.454C>T)?

AlphaMissense predicts likely benign (score 0.0806) — an in-silico prediction, not a clinical call.

KIF2A p.Pro152Ser

c.454C>T · rs759771074 · VCV3234930

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0806 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

complex cortical dysplasia with other brain malformations 3

Computational evidence

Protein change
AlphaMissense	0.0806	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -5.82	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 6	phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 9,781 bp · p 5.2e-18 · regional, not allelic
Overall
CADD	21.7	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

Grpmax group 0.0011% South Asian · 1/90,538 alleles

Overall 6.21e-05% 1/1,609,684 alleles · very rare exomes 1/1,457,542 · genomes 0/152,142 · 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: KIF2A
Protein: p.Pro152Ser
Coding: c.454C>T
MANE Select: NM_001098511
dbSNP: rs759771074
Type: single nucleotide variant
Location: chr5:62352707 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.76 (gnomAD)
Structure: AlphaFold pLDDT 79.37 · 6 PDB
Residue 152: the 'globular' region

Full KIF2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

complex cortical dysplasia with other brain malformations 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KIF2A p.Pro152= Uncertain significance ★ same residue
KIF2A p.Glu73Lys Likely pathogenic ★★ ⚠ same condition
KIF2A p.Gly313Glu Likely pathogenic ★★ same condition
KIF2A p.Ser317Asn Pathogenic ★★ same condition
KIF2A p.Thr320Ile Pathogenic/Likely pathogenic ★★ same condition
KIF2A p.Lys319Arg Uncertain significance ★★ ⚠ same condition
KIF2A c.1027+21A>T Benign ★★ same condition
KIF2A c.65-20T>C 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/kif2a-p-pro152ser (accessed [today's date]).

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