Is KANK1 p.Ala1237fs (c.3709del) pathogenic?

KANK1 p.Ala1237fs (c.3709del) is classified Uncertain significance in KANK1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-28). Ultra-rare (popmax 0.0117%, amr); Associated with cerebral palsy, spastic quadriplegic, 2.

What condition is associated with KANK1 p.Ala1237fs (c.3709del)?

KANK1 p.Ala1237fs (c.3709del) is associated with cerebral palsy, spastic quadriplegic, 2 (ClinVar).

How common is KANK1 p.Ala1237fs (c.3709del) in the general population?

KANK1 p.Ala1237fs (c.3709del) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

How is Inherited congenital spastic tetraplegia inherited?

Typically Autosomal recessive, Unknown (Orphanet). A genetic counselor can assess individual risk for a family.

KANK1 p.Ala1237fs

c.3709del · rs758879616 · VCV1033739

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

cerebral palsy, spastic quadriplegic, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,010 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00062% 10/1,614,038 alleles · ultra-rare exomes 10/1,461,702 · genomes 0/152,336 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,573
Remaining individualsnot grpmax-eligible	0.0016%	62,504
African / African-American	0.00133%	75,062
European (non-Finnish)	8.48e-05%	1,179,920

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: KANK1
Protein: p.Ala1237fs
Coding: c.3709del
MANE Select: NM_015158
dbSNP: rs758879616
Type: Deletion
Location: chr9:742216 (GRCh38)
Gene constraint: LOEUF 1.149 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.50 · 5 PDB
Residue 1237: the 'interaction with kif21a' region; an α-helix

Full KANK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cerebral palsy, spastic quadriplegic, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Inherited congenital spastic tetraplegia (Orphanet):

Inheritance: Autosomal recessive, Unknown
Onset: Infancy, Neonatal

Similar variants

KANK1 p.Glu608del Uncertain significance ★★ same condition
KANK1 p.Lys1212del Uncertain significance ★★ same condition
KANK1 p.Ala1237Val Uncertain significance ★ ⚠ same residue
KANK1 p.Gln331fs Uncertain significance ★ same condition
KANK1 c.3554-9_3554-5del Benign ★ same condition
KANK1 c.2896+2T>G Uncertain significance ★★ same condition
KANK1 p.Ala1184= Uncertain significance ★★ same condition
KANK1 p.Ala1203Val Uncertain significance ★★ ⚠ 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/kank1-p-ala1237fs (accessed [today's date]).

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