Is CCT6A p.Pro427Arg (c.1280C>G) pathogenic?

CCT6A p.Pro427Arg (c.1280C>G) is classified Uncertain significance in CCT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-21). AlphaMissense: likely benign (0.1173); Absent from gnomAD v4.1.

How common is CCT6A p.Pro427Arg (c.1280C>G) in the general population?

CCT6A p.Pro427Arg (c.1280C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCT6A p.Pro427Arg (c.1280C>G)?

AlphaMissense predicts likely benign (score 0.1173) — an in-silico prediction, not a clinical call.

CCT6A p.Pro427Arg

c.1280C>G · VCV3997877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1173 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1173	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -9.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	phastCons 0.15
Regional constraint	o/e 0.81	unconstrained · MANE · 5,082 bp · p 0.00016 · regional, not allelic
Overall
CADD	18.75	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

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: CCT6A
Protein: p.Pro427Arg
Coding: c.1280C>G
MANE Select: NM_001762
Type: single nucleotide variant
Location: chr7:56060873 (GRCh38)
Gene constraint: LOEUF 0.234 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 71 PDB
Residue 427: an α-helix

Full CCT6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT6A p.Ser473= Benign ★★ same type
CCT6A c.1450+1G>A Uncertain significance ★ same type
CCT6A p.Ala14Val Uncertain significance ★ ⚠ same type
CCT6A p.Ala253Val Uncertain significance ★ same type
CCT6A p.Ala2Pro Uncertain significance ★ ⚠ same type
CCT6A p.Ala401Gly Uncertain significance ★ ⚠ same type
CCT6A p.Ala452Ser Uncertain significance ★ ⚠ same type
CCT6A p.Ala452Val 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/cct6a-p-pro427arg (accessed [today's date]).

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