Is KIF2A p.Asp187= (c.561C>T) pathogenic?

KIF2A p.Asp187= (c.561C>T) is classified Likely benign in KIF2A (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-20). Very rare (popmax 0.00559%, afr).

How common is KIF2A p.Asp187= (c.561C>T) in the general population?

KIF2A p.Asp187= (c.561C>T) is very rare (popmax 0.00559%, afr) (gnomAD).

KIF2A p.Asp187=

c.561C>T · rs1330714767 · VCV3022518

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00559%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.89	phastCons 1
Overall
CADD	11.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00559% African / African-American · 4/71,554 alleles

Filtering AF 0.0019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.000824% 12/1,456,696 alleles · very rare exomes 10/1,304,624 · genomes 2/152,072 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00699%	14,304
African / African-Americangrpmax	0.00559%	17,889
South Asian	0.00351%	28,521
East Asian	0.00228%	43,836

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp187=
Coding: c.561C>T
MANE Select: NM_001098511
dbSNP: rs1330714767
Type: single nucleotide variant
Location: chr5:62355161 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.76 (gnomAD)
Structure: AlphaFold pLDDT 79.37 · 6 PDB
Residue 187: the 'globular' 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-asp187 (accessed [today's date]).

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