What condition is associated with CCT5 c.331+71T>C?

CCT5 c.331+71T>C is associated with hereditary sensory and autonomic neuropathy with spastic paraplegia (ClinVar).

CCT5 c.331+71T>C

Q: Is CCT5 c.331+71T>C pathogenic?

CCT5 c.331+71T>C is classified Benign in CCT5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-07-14). Common (popmax 88.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with hereditary sensory and autonomic neuropathy with spastic paraplegia.

Q: How common is CCT5 c.331+71T>C in the general population?

CCT5 c.331+71T>C is common (popmax 88.9%, 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.

rs2607294 · VCV1192658

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 88.9%, 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
Splice region	donor +71	deep intronic (+71 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -2.6
Overall
CADD	0.072	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 88.9% East Asian · 38,379/43,180 alleles

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

Overall 82.2% 1,046,090/1,273,188 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	88.9%	1
Ashkenazi Jewishnot grpmax-eligible	87.3%	1
Finnishnot grpmax-eligible	86.2%	1
European (non-Finnish)	85.8%	1
Amishnot grpmax-eligible	83.8%	1
Remaining individualsnot grpmax-eligible	82.2%	1
Admixed American	80.3%	1
Middle Eastern	79.3%	1
South Asian	66.5%	2
African / African-American	46.1%	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.331+71T>C
MANE Select: NM_012073
dbSNP: rs2607294
Type: single nucleotide variant
Location: chr5:10254909 (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-331-plus-71t-c (accessed [today's date]).

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