Is CCT2 p.Ser60Pro (c.178T>C) pathogenic?

CCT2 p.Ser60Pro (c.178T>C) is classified Uncertain significance in CCT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-24). AlphaMissense: likely benign (0.1391); Absent from gnomAD v4.1.

How common is CCT2 p.Ser60Pro (c.178T>C) in the general population?

CCT2 p.Ser60Pro (c.178T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCT2 p.Ser60Pro (c.178T>C)?

AlphaMissense predicts likely benign (score 0.1391) — an in-silico prediction, not a clinical call.

CCT2 p.Ser60Pro

c.178T>C · rs1881702085 · VCV1354207

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1391 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1391	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -10.50	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 7,571 bp · p 0.023 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCT2
Protein: p.Ser60Pro
Coding: c.178T>C
MANE Select: NM_006431
dbSNP: rs1881702085
Type: single nucleotide variant
Location: chr12:69587538 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.85 · 71 PDB
Residue 60: a modified residue (phosphoserine)

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-ser60pro (accessed [today's date]).

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