Is CCT2 p.Pro229fs (c.685_688del) pathogenic?

CCT2 p.Pro229fs (c.685688del) is classified Uncertain significance in CCT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-22). Very rare (popmax 0.000257%, nfe).

How common is CCT2 p.Pro229fs (c.685_688del) in the general population?

CCT2 p.Pro229fs (c.685_688del) is very rare (popmax 0.000257%, nfe) (gnomAD).

CCT2 p.Pro229fs

c.685_688del · VCV4917577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000257%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 8 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP 2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000257% European (non-Finnish) · 3/1,167,080 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000188% 3/1,599,768 alleles · very rare exomes 3/1,447,510 · genomes 0/152,258 · joint denominator

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.Pro229fs
Coding: c.685_688del
MANE Select: NM_006431
Type: Deletion
Location: chr12:69592091 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.85 · 71 PDB

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

Similar variants

CCT2 p.Pro229Leu Uncertain significance ★ ⚠ same residue
CCT2 c.1232-3del Uncertain significance ★ same type
CCT2 p.Glu350fs Uncertain significance ★ same type
CCT2 p.Lys276fs Uncertain significance ★ same type
CCT2 c.1436-8_1436-6del Likely benign ★ same type
CCT2 c.144+22_144+40del Benign ★ same type
CCT2 c.1577+15_1577+16del Likely benign ★ same type
CCT2 c.4-8del Likely benign ★ 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-pro229fs (accessed [today's date]).

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