Is CCT6A p.Ala2Pro (c.4G>C) pathogenic?

CCT6A p.Ala2Pro (c.4G>C) is classified Uncertain significance in CCT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-29). AlphaMissense: ambiguous (0.5246); No allele count reported in gnomAD v4.1 (AN 1,559,736).

How common is CCT6A p.Ala2Pro (c.4G>C) in the general population?

CCT6A p.Ala2Pro (c.4G>C) is no allele count reported in gnomAD v4.1 (AN 1,559,736) (gnomAD).

What do computational predictors say about CCT6A p.Ala2Pro (c.4G>C)?

AlphaMissense predicts ambiguous (score 0.5246) — an in-silico prediction, not a clinical call.

CCT6A p.Ala2Pro

c.4G>C · VCV4650305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5246 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,559,736)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5246	ambiguous
REVEL	0.215	benign-leaning
SaProt	LLR -9.18	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 3,877 bp · p 4.6e-07 · regional, not allelic
Overall
CADD	22.5	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

No allele count reported in gnomAD v4.1 (AN 1,559,736). 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: CCT6A
Protein: p.Ala2Pro
Coding: c.4G>C
MANE Select: NM_001762
Type: single nucleotide variant
Location: chr7:56051852 (GRCh38)
Gene constraint: LOEUF 0.234 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 71 PDB
Residue 2: a modified residue (n-acetylalanine)

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.Ala401Gly Uncertain significance ★ ⚠ same type
CCT6A p.Ala452Ser Uncertain significance ★ ⚠ same type
CCT6A p.Ala452Val Uncertain significance ★ ⚠ same type
CCT6A p.Ala468Gly 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-ala2pro (accessed [today's date]).

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