Is KANK1 p.Val511= (c.1533T>C) pathogenic?

KANK1 p.Val511= (c.1533T>C) is classified Likely benign in KANK1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-10). Ultra-rare (popmax 0.0383%, amr); Associated with cerebral palsy, spastic quadriplegic, 2.

What condition is associated with KANK1 p.Val511= (c.1533T>C)?

KANK1 p.Val511= (c.1533T>C) is associated with cerebral palsy, spastic quadriplegic, 2 (ClinVar).

How common is KANK1 p.Val511= (c.1533T>C) in the general population?

KANK1 p.Val511= (c.1533T>C) is ultra-rare (popmax 0.0383%, 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.Val511=

c.1533T>C · rs199881654 · VCV782524

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, amr)

Conditions

cerebral palsy, spastic quadriplegic, 2

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 -1.6	GERP -5.3
Overall
CADD	0.476	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0383% Admixed American · 23/60,014 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.00347% 56/1,614,100 alleles · ultra-rare exomes 36/1,461,890 · genomes 20/152,210 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0383%	2,609
Remaining individualsnot grpmax-eligible	0.0176%	5,683
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.00178%	56,191

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.Val511=
Coding: c.1533T>C
MANE Select: NM_015158
dbSNP: rs199881654
Type: single nucleotide variant
Location: chr9:712299 (GRCh38)
Gene constraint: LOEUF 1.149 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.50 · 5 PDB

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 c.2896+2T>G Uncertain significance ★★ same condition
KANK1 p.Ala1184= Uncertain significance ★★ same condition
KANK1 p.Ala1203Val Uncertain significance ★★ ⚠ same condition
KANK1 p.Ala1255Asp Uncertain significance ★★ ⚠ same condition
KANK1 p.Ala228Gly Uncertain significance ★★ ⚠ same condition
KANK1 p.Ala718Gly Uncertain significance ★★ ⚠ same condition
KANK1 p.Arg420Ser Uncertain significance ★★ ⚠ same condition
KANK1 p.Arg471His 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-val511 (accessed [today's date]).

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