Is KIF2A p.Ser129Pro (c.385T>C) pathogenic?

KIF2A p.Ser129Pro (c.385T>C) is classified Uncertain significance in KIF2A (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-19). AlphaMissense: likely benign (0.0694); Absent from gnomAD v4.1.

How common is KIF2A p.Ser129Pro (c.385T>C) in the general population?

KIF2A p.Ser129Pro (c.385T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIF2A p.Ser129Pro (c.385T>C)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

KIF2A p.Ser129Pro

c.385T>C · rs2111924785 · VCV1203497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -6.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.53	gain · loss 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 5.2	phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 5,543 bp · p 0.017 · regional, not allelic
Overall
CADD	22.2	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: KIF2A
Protein: p.Ser129Pro
Coding: c.385T>C
MANE Select: NM_001098511
dbSNP: rs2111924785
Type: single nucleotide variant
Location: chr5:62352638 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.76 (gnomAD)
Structure: AlphaFold pLDDT 79.37 · 6 PDB
Residue 129: the 'globular' region; the 'disordered' region

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

Similar variants

KIF2A p.Glu73Lys Likely pathogenic ★★ ⚠ same type
KIF2A p.Gly313Glu Likely pathogenic ★★ same type
KIF2A p.Ser317Asn Pathogenic ★★ same type
KIF2A p.Thr320Ile Pathogenic/Likely pathogenic ★★ same type
KIF2A p.Ala144Thr Uncertain significance ★★ ⚠ same type
KIF2A p.Arg117His Uncertain significance ★★ ⚠ same type
KIF2A p.Arg154His Uncertain significance ★★ ⚠ same type
KIF2A p.Arg402Trp 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/kif2a-p-ser129pro (accessed [today's date]).

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