Is CCT5 p.Leu313fs (c.936_937del) pathogenic?

CCT5 p.Leu313fs (c.936937del) is classified Uncertain significance in CCT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). Associated with hereditary sensory and autonomic neuropathy with spastic paraplegia.

What condition is associated with CCT5 p.Leu313fs (c.936_937del)?

CCT5 p.Leu313fs (c.936_937del) is associated with hereditary sensory and autonomic neuropathy with spastic paraplegia (ClinVar).

CCT5 p.Leu313fs

Q: How is Mutilating hereditary sensory neuropathy with spastic paraplegia inherited?

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

c.936_937del · VCV3649193

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary sensory and autonomic neuropathy with spastic paraplegia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 7 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1

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

Variant & gene context

Gene: CCT5
Protein: p.Leu313fs
Coding: c.936_937del
MANE Select: NM_012073
Type: Deletion
Location: chr5:10260854 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.34 · 75 PDB
Residue 313: an α-helix

Full CCT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary sensory and autonomic neuropathy with spastic paraplegia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mutilating hereditary sensory neuropathy with spastic paraplegia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

CCT5 c.1498+28del Benign ★★ same condition
CCT5 c.1498+36_1498+38del Benign ★★ same condition
CCT5 c.166+8del Conflicting classifications of pathogenicity ★ same condition
CCT5 c.332-19_332-16del Benign ★ same condition
CCT5 c.531-3C>T Uncertain significance ★★ same condition
CCT5 c.*1126T>A Uncertain significance ★★ same condition
CCT5 c.*567G>A Uncertain significance ★★ same condition
CCT5 p.Ala246Val 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/cct5-p-leu313fs (accessed [today's date]).

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