Is CCT3 p.Arg16Cys (c.46C>T) pathogenic?

CCT3 p.Arg16Cys (c.46C>T) is classified Uncertain significance in CCT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-26). AlphaMissense: likely pathogenic (0.9639); Very rare (popmax 0.00223%, eas).

How common is CCT3 p.Arg16Cys (c.46C>T) in the general population?

CCT3 p.Arg16Cys (c.46C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CCT3 p.Arg16Cys (c.46C>T)?

AlphaMissense predicts likely pathogenic (score 0.9639) — an in-silico prediction, not a clinical call.

CCT3 p.Arg16Cys

c.46C>T · rs947249193 · VCV2369698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9639 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9639	likely pathogenic
REVEL	0.472	indeterminate
SaProt	LLR -13.92	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 29 kb · p 0.0019 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.00223% East Asian · 1/44,896 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,613,852 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,896
Finnishnot grpmax-eligible	0.00156%	64,032
European (non-Finnish)	0.000678%	147,488

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.Arg16Cys
Coding: c.46C>T
MANE Select: NM_005998
dbSNP: rs947249193
Type: single nucleotide variant
Location: chr1:156335874 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.23 · 72 PDB
Residue 16: the 'disordered' region; a β-strand

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.Arg230Gln Uncertain significance ★ ⚠ same type
CCT3 p.Arg230Trp Uncertain significance ★ ⚠ same type
CCT3 p.Arg313His 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-arg16cys (accessed [today's date]).

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