Is CCT5 p.Glu484Val (c.1451A>T) pathogenic?

CCT5 p.Glu484Val (c.1451A>T) is classified Uncertain significance in CCT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-07). AlphaMissense: likely benign (0.3173); Very rare (popmax 8.47e-05%, nfe).

How common is CCT5 p.Glu484Val (c.1451A>T) in the general population?

CCT5 p.Glu484Val (c.1451A>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CCT5 p.Glu484Val (c.1451A>T)?

AlphaMissense predicts likely benign (score 0.3173) — an in-silico prediction, not a clinical call.

CCT5 p.Glu484Val

c.1451A>T · rs2477474075 · VCV2558877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3173 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3173	likely benign
REVEL	0.706	pathogenic-leaning
SaProt	LLR -14.05	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 1,587 bp · p 0.33 · regional, not allelic
Overall
CADD	27.5	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,958 alleles

Overall 6.84e-05% 1/1,461,688 alleles · very rare

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: CCT5
Protein: p.Glu484Val
Coding: c.1451A>T
MANE Select: NM_012073
dbSNP: rs2477474075
Type: single nucleotide variant
Location: chr5:10263267 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.34 · 75 PDB

Full CCT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT5 c.531-3C>T Uncertain significance ★★ same type
CCT5 c.*1126T>A Uncertain significance ★★ same type
CCT5 c.*567G>A Uncertain significance ★★ same type
CCT5 p.Ala246Val Uncertain significance ★★ ⚠ same type
CCT5 p.Ala41Gly Uncertain significance ★★ ⚠ same type
CCT5 p.Ala424Ser Uncertain significance ★★ ⚠ same type
CCT5 p.Arg142Cys Uncertain significance ★★ ⚠ same type
CCT5 p.Arg400Leu 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/cct5-p-glu484val (accessed [today's date]).

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