Is CCT5 p.Gln472His (c.1416G>C) pathogenic?

CCT5 p.Gln472His (c.1416G>C) is classified Uncertain significance in CCT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.2247); Absent from gnomAD v4.1.

How common is CCT5 p.Gln472His (c.1416G>C) in the general population?

CCT5 p.Gln472His (c.1416G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCT5 p.Gln472His (c.1416G>C)?

AlphaMissense predicts likely benign (score 0.2247) — an in-silico prediction, not a clinical call.

CCT5 p.Gln472His

c.1416G>C · VCV4650301

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2247 · 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	0.2247	likely benign
REVEL	0.425	indeterminate
SaProt	LLR -7.49	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 6.5	GERP 0.71, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 1,587 bp · p 0.33 · regional, not allelic
Overall
CADD	22.8	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: CCT5
Protein: p.Gln472His
Coding: c.1416G>C
MANE Select: NM_012073
Type: single nucleotide variant
Location: chr5:10263232 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.34 · 75 PDB
Residue 472: an α-helix

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-gln472his (accessed [today's date]).

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