Is KIF4A p.Pro552= (c.1656C>T) pathogenic?

KIF4A p.Pro552= (c.1656C>T) is classified Benign in KIF4A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-07). Common (popmax 35%, afr) — too common for a highly-penetrant pathogenic allele; Associated with KIF4A-related disorder.

What condition is associated with KIF4A p.Pro552= (c.1656C>T)?

KIF4A p.Pro552= (c.1656C>T) is associated with KIF4A-related disorder (ClinVar).

KIF4A p.Pro552=

Q: How common is KIF4A p.Pro552= (c.1656C>T) in the general population?

KIF4A p.Pro552= (c.1656C>T) is common (popmax 35%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1656C>T · rs1199429 · VCV3055648

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 35%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

KIF4A-related disorder

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 0.21	GERP -2.9, phastCons 0.97
Overall
CADD	5.715	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 35% African / African-American · 19,679/56,269 alleles

Filtering AF 34.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 34.4%

Overall 5.51% 65,202/1,182,801 alleles · common exomes 51,171/1,071,313 · genomes 14,031/111,488 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	35%	3
Middle Eastern	8.98%	11
Ashkenazi Jewishnot grpmax-eligible	7.49%	13
Remaining individualsnot grpmax-eligible	6.2%	16
Admixed American	4.83%	21
European (non-Finnish)	4.13%	24
Finnishnot grpmax-eligible	2.33%	43
South Asian	2.29%	44
Amishnot grpmax-eligible	0.584%	171
East Asian	0.00913%	10,948

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: KIF4A
Protein: p.Pro552=
Coding: c.1656C>T
MANE Select: NM_012310
dbSNP: rs1199429
Type: single nucleotide variant
Location: chrX:70353789 (GRCh38)
Structure: AlphaFold pLDDT 71.70 · 1 PDB

Full KIF4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KIF4A-related disorder

Similar variants

KIF4A p.Arg1118Gln Uncertain significance ★★ ⚠ same condition
KIF4A p.Ser1219Thr Uncertain significance ★★ ⚠ same condition
KIF4A p.Asn530His Uncertain significance ★ same condition
KIF4A p.Ala1215Asp Uncertain significance ⚠ same condition
KIF4A p.Phe909Leu Uncertain significance ⚠ same condition
KIF4A c.1489-7T>C Likely benign same condition
KIF4A p.Ile1227= Likely benign same condition
KIF4A p.Leu422Trp 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/kif4a-p-pro552 (accessed [today's date]).

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