Is CCT2 p.Ala378= (c.1134C>T) pathogenic?

CCT2 p.Ala378= (c.1134C>T) is classified Likely benign in CCT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Very rare (popmax 8.48e-05%, nfe).

How common is CCT2 p.Ala378= (c.1134C>T) in the general population?

CCT2 p.Ala378= (c.1134C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CCT2 p.Ala378=

c.1134C>T · rs1223649257 · VCV1602798

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 -0.22	GERP 0.11, phastCons 0.25
Overall
CADD	9.995	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,828 alleles

Overall 6.84e-05% 1/1,461,594 alleles · very rare

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: CCT2
Protein: p.Ala378=
Coding: c.1134C>T
MANE Select: NM_006431
dbSNP: rs1223649257
Type: single nucleotide variant
Location: chr12:69597669 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.85 · 71 PDB
Residue 378: a β-strand

Full CCT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT2 p.Ala128Thr Uncertain significance ★★ ⚠ same type
CCT2 p.Ala133Val Uncertain significance ★★ ⚠ same type
CCT2 p.Ala145Val Uncertain significance ★★ ⚠ same type
CCT2 p.Arg156Cys Uncertain significance ★★ ⚠ same type
CCT2 p.Arg255Gln Uncertain significance ★★ ⚠ same type
CCT2 p.Arg255Trp Uncertain significance ★★ ⚠ same type
CCT2 p.Arg281Cys Uncertain significance ★★ ⚠ same type
CCT2 p.Arg281His 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/cct2-p-ala378 (accessed [today's date]).

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