Is CCT3 p.Gln73Arg (c.218A>G) pathogenic?

CCT3 p.Gln73Arg (c.218A>G) is classified Uncertain significance in CCT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: ambiguous (0.4965); Very rare (popmax 6.84e-05%).

How common is CCT3 p.Gln73Arg (c.218A>G) in the general population?

CCT3 p.Gln73Arg (c.218A>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about CCT3 p.Gln73Arg (c.218A>G)?

AlphaMissense predicts ambiguous (score 0.4965) — an in-silico prediction, not a clinical call.

CCT3 p.Gln73Arg

c.218A>G · VCV3487665

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4965 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Computational evidence

Protein change
AlphaMissense	0.4965	ambiguous
REVEL	0.528	indeterminate
SaProt	LLR -12.89	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 29 kb · p 0.0019 · regional, not allelic
Overall
CADD	25.5	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 6.84e-05%

Overall 6.84e-05% 1/1,461,532 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: CCT3
Protein: p.Gln73Arg
Coding: c.218A>G
MANE Select: NM_005998
Type: single nucleotide variant
Location: chr1:156333633 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.23 · 72 PDB

Full CCT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT3 p.Ala307Thr Uncertain significance ★ ⚠ same type
CCT3 p.Ala421Gly Uncertain significance ★ ⚠ same type
CCT3 p.Ala457Ser Uncertain significance ★ ⚠ same type
CCT3 p.Arg127Cys Uncertain significance ★ ⚠ same type
CCT3 p.Arg167Gln Uncertain significance ★ ⚠ same type
CCT3 p.Arg16Cys Uncertain significance ★ ⚠ same type
CCT3 p.Arg230Gln Uncertain significance ★ ⚠ same type
CCT3 p.Arg230Trp 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/cct3-p-gln73arg (accessed [today's date]).

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