Is KIF4A p.Pro9= (c.27C>T) pathogenic?

KIF4A p.Pro9= (c.27C>T) is classified Benign in KIF4A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-08-19). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with intellectual disability, X-linked 100.

What condition is associated with KIF4A p.Pro9= (c.27C>T)?

KIF4A p.Pro9= (c.27C>T) is associated with intellectual disability, X-linked 100 (ClinVar).

KIF4A p.Pro9=

Q: How common is KIF4A p.Pro9= (c.27C>T) in the general population?

KIF4A p.Pro9= (c.27C>T) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.27C>T · rs1199470 · VCV1300073

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

intellectual disability, X-linked 100

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.73 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.056	GERP -2.8, phastCons 0.85
Overall
CADD	11.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 33,658/33,660 alleles

Filtering AF 99.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.9%

Overall 99.1% 1,196,998/1,208,113 alleles · common exomes 1,087,665/1,097,926 · genomes 109,333/110,187 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	100%	1
East Asiangrpmax	100%	1
Finnishnot grpmax-eligible	99.9%	1
African / African-American	99.9%	1
South Asian	99.8%	1
Admixed American	99.2%	1
Remaining individualsnot grpmax-eligible	99.1%	1
European (non-Finnish)	99%	1
Middle Eastern	98.4%	1
Ashkenazi Jewishnot grpmax-eligible	96.8%	1

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: KIF4A
Protein: p.Pro9=
Coding: c.27C>T
MANE Select: NM_012310
dbSNP: rs1199470
Type: single nucleotide variant
Location: chrX:70290485 (GRCh38)
Structure: AlphaFold pLDDT 71.70 · 1 PDB
Residue 9: the kinesin motor domain

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

Disease context

intellectual disability, X-linked 100 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KIF4A p.Arg641Trp Uncertain significance ★★ ⚠ same condition
KIF4A p.Arg652His Uncertain significance ★★ ⚠ same condition
KIF4A p.Asn304Ser Uncertain significance ★★ ⚠ same condition
KIF4A p.Asp509Asn Uncertain significance ★★ ⚠ same condition
KIF4A p.Glu705Lys Uncertain significance ★★ same condition
KIF4A p.Gly375Arg Uncertain significance ★★ ⚠ same condition
KIF4A c.3073-4C>T Benign ★★ same condition
KIF4A c.3372+11G>T 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-pro9 (accessed [today's date]).

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