Is CCT5 p.Arg142= (c.426T>C) pathogenic?

CCT5 p.Arg142= (c.426T>C) is classified Benign in CCT5 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Common (popmax 89.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with hereditary sensory and autonomic neuropathy with spastic paraplegia.

What condition is associated with CCT5 p.Arg142= (c.426T>C)?

CCT5 p.Arg142= (c.426T>C) is associated with hereditary sensory and autonomic neuropathy with spastic paraplegia (ClinVar).

CCT5 p.Arg142=

Q: How common is CCT5 p.Arg142= (c.426T>C) in the general population?

CCT5 p.Arg142= (c.426T>C) is common (popmax 89.1%, 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.

c.426T>C · rs1042392 · VCV350249

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 89.1%, 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 0.18	GERP -5.1, phastCons 0.93
Overall
CADD	10.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 89.1% East Asian · 40,015/44,886 alleles

Filtering AF 88.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 88.1%

Overall 83.2% 1,342,495/1,613,930 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	89.1%	1
Ashkenazi Jewishnot grpmax-eligible	87.3%	1
European (non-Finnish)	86.4%	1
Finnishnot grpmax-eligible	86.2%	1
Amishnot grpmax-eligible	84.2%	1
Remaining individualsnot grpmax-eligible	82.6%	1
Admixed American	80.6%	1
Middle Eastern	79.1%	1
South Asian	66.6%	2
African / African-American	47.1%	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
Protein: p.Arg142=
Coding: c.426T>C
MANE Select: NM_012073
dbSNP: rs1042392
Type: single nucleotide variant
Location: chr5:10256049 (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 142: 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 p.Arg142Cys Uncertain significance ★★ ⚠ same residue
CCT5 p.Arg142His Uncertain significance ★ ⚠ same residue
CCT5 p.Arg142Leu Uncertain significance ★ ⚠ same residue
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

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-arg142 (accessed [today's date]).

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