Is KIF23 p.Pro495= (c.1485A>G) pathogenic?

KIF23 p.Pro495= (c.1485A>G) is classified Benign/Likely benign in KIF23 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 97.3%, nfe) — too common for a highly-penetrant pathogenic allele.

KIF23 p.Pro495=

Q: How common is KIF23 p.Pro495= (c.1485A>G) in the general population?

KIF23 p.Pro495= (c.1485A>G) is common (popmax 97.3%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1485A>G · rs3825858 · VCV1251717

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 97.3%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.2	GERP -4.1
Overall
CADD	1.291	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 97.3% European (non-Finnish) · 1,147,415/1,179,010 alleles

Filtering AF 97.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 97.1%

Overall 93.6% 1,509,190/1,612,434 alleles · common exomes 1,381,168/1,460,308 · genomes 128,022/152,126 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	97.6%	1
European (non-Finnish)grpmax	97.3%	1
Ashkenazi Jewishnot grpmax-eligible	97.2%	1
South Asian	95.7%	1
Middle Eastern	94.2%	1
Finnishnot grpmax-eligible	93%	1
Remaining individualsnot grpmax-eligible	92.5%	1
Admixed American	76.3%	1
East Asian	69.5%	1
African / African-American	60.5%	2

Amish 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: KIF23
Protein: p.Pro495=
Coding: c.1485A>G
MANE Select: NM_001367805
dbSNP: rs3825858
Type: single nucleotide variant
Location: chr15:69436610 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.08 · 1 PDB

Full KIF23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KIF23 p.Pro495Leu Uncertain significance ★ same residue
KIF23 c.1930-3T>C Uncertain significance ★★ same type
KIF23 p.Ala330Thr Uncertain significance ★★ ⚠ same type
KIF23 p.Ala816Thr Uncertain significance ★★ ⚠ same type
KIF23 p.Arg134Cys Uncertain significance ★★ ⚠ same type
KIF23 p.Arg173Cys Uncertain significance ★★ ⚠ same type
KIF23 p.Arg173His Uncertain significance ★★ ⚠ same type
KIF23 p.Arg310Cys 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/kif23-p-pro495 (accessed [today's date]).

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