CCT5 c.*181C>T

Q: Is CCT5 c.*181C>T pathogenic?

CCT5 c.181C>T is classified Benign in CCT5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-06-18). Common (popmax 89%, eas) — too common for a highly-penetrant pathogenic allele; Associated with hereditary sensory and autonomic neuropathy with spastic paraplegia.

Q: What condition is associated with CCT5 c.*181C>T?

CCT5 c.*181C>T is associated with hereditary sensory and autonomic neuropathy with spastic paraplegia (ClinVar).

Q: How common is CCT5 c.*181C>T in the general population?

CCT5 c.*181C>T is common (popmax 89%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.

rs699113 · VCV350264

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 89%, eas) — too common for a highly-penetrant pathogenic allele

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.96	GERP -4.2
Overall
CADD	0.892	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 89% East Asian · 31,906/35,868 alleles

Filtering AF 88.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 87.8%

Overall 80.4% 547,813/681,050 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	89%	1
Ashkenazi Jewishnot grpmax-eligible	87.5%	1
Finnishnot grpmax-eligible	86.1%	1
European (non-Finnish)	85.2%	1
Amishnot grpmax-eligible	83.7%	1
Remaining individualsnot grpmax-eligible	81.5%	1
Admixed American	80.2%	1
Middle Eastern	78%	1
South Asian	66.2%	2
African / African-American	46.5%	2

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: CCT5
Coding: c.*181C>T
MANE Select: NM_012073
dbSNP: rs699113
Type: single nucleotide variant
Location: chr5:10264964 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.34 · 75 PDB

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.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
CCT5 p.Ala41Gly Uncertain significance ★★ ⚠ same condition
CCT5 p.Ala424Ser Uncertain significance ★★ ⚠ same condition
CCT5 p.Arg142Cys Uncertain significance ★★ ⚠ same condition
CCT5 p.Arg400Leu 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-c-star-181c-t (accessed [today's date]).

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