Is CCT2 p.Pro447Thr (c.1339C>A) pathogenic?

CCT2 p.Pro447Thr (c.1339C>A) is classified Uncertain significance in CCT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely pathogenic (0.8993); Absent from gnomAD v4.1.

How common is CCT2 p.Pro447Thr (c.1339C>A) in the general population?

CCT2 p.Pro447Thr (c.1339C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCT2 p.Pro447Thr (c.1339C>A)?

AlphaMissense predicts likely pathogenic (score 0.8993) — an in-silico prediction, not a clinical call.

CCT2 p.Pro447Thr

c.1339C>A · rs2499012363 · VCV2086050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8993 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,578,812)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8993	likely pathogenic
REVEL	0.699	pathogenic-leaning
SaProt	LLR -12.24	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 4,143 bp · p 0.12 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,578,812). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CCT2
Protein: p.Pro447Thr
Coding: c.1339C>A
MANE Select: NM_006431
dbSNP: rs2499012363
Type: single nucleotide variant
Location: chr12:69598325 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.85 · 71 PDB
Residue 447: an α-helix

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

Similar variants

CCT2 p.Pro447Leu Uncertain significance ★ ⚠ same residue
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

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-pro447thr (accessed [today's date]).

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