Is CCT5 c.993+42C>T pathogenic?

CCT5 c.993+42C>T is classified Benign in CCT5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-18). Common (popmax 13.8%, sas) — too common for a highly-penetrant pathogenic allele.

CCT5 c.993+42C>T

Q: How common is CCT5 c.993+42C>T in the general population?

CCT5 c.993+42C>T is common (popmax 13.8%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs12516390 · VCV1248657

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 13.8%, sas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +42	near-intronic (+42 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.71	GERP -2.2
Non-coding constraint	Z 1.99	1 kb window · o/e 0.77 · regional · uncalibrated
Overall
CADD	8.936	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.8% South Asian · 12,583/90,854 alleles

Filtering AF 13.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.6%

Overall 6.96% 112,002/1,608,182 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	13.8%	7
Admixed American	11.9%	8
Amishnot grpmax-eligible	8.88%	11
European (non-Finnish)	6.97%	14
Middle Eastern	6.69%	15
Finnishnot grpmax-eligible	6.22%	16
Remaining individualsnot grpmax-eligible	6.15%	16
Ashkenazi Jewishnot grpmax-eligible	3.84%	26
African / African-American	1.18%	85
East Asian	0.0647%	1,545

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.993+42C>T
MANE Select: NM_012073
dbSNP: rs12516390
Type: single nucleotide variant
Location: chr5:10260953 (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

Similar variants

CCT5 c.531-3C>T Uncertain significance ★★ same type
CCT5 c.*1126T>A Uncertain significance ★★ same type
CCT5 c.*567G>A Uncertain significance ★★ same type
CCT5 p.Ala246Val Uncertain significance ★★ ⚠ same type
CCT5 p.Ala41Gly Uncertain significance ★★ ⚠ same type
CCT5 p.Ala424Ser Uncertain significance ★★ ⚠ same type
CCT5 p.Arg142Cys Uncertain significance ★★ ⚠ same type
CCT5 p.Arg400Leu Uncertain significance ★★ ⚠ same type

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-993-plus-42c-t (accessed [today's date]).

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