Is CCT4 p.Arg483Gln (c.1448G>A) pathogenic?

CCT4 p.Arg483Gln (c.1448G>A) is classified Uncertain significance in CCT4 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-09-17). AlphaMissense: likely benign (0.1519); Low-frequency (popmax 1.59%, mid).

How common is CCT4 p.Arg483Gln (c.1448G>A) in the general population?

CCT4 p.Arg483Gln (c.1448G>A) is low-frequency (popmax 1.59%, mid) (gnomAD).

What do computational predictors say about CCT4 p.Arg483Gln (c.1448G>A)?

AlphaMissense predicts likely benign (score 0.1519) — an in-silico prediction, not a clinical call.

CCT4 p.Arg483Gln

c.1448G>A · rs146765948 · VCV2393526

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1519 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.59%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1519	likely benign
REVEL	0.384	indeterminate
SaProt	LLR -11.47	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 15 kb · p 0.04 · regional, not allelic
Overall
CADD	24.2	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 1.59% Middle Eastern · 95/5,974 alleles

Filtering AF 1.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.24%

Overall 0.0842% 1,359/1,613,854 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.59%	63
Ashkenazi Jewishnot grpmax-eligible	0.463%	216
Remaining individualsnot grpmax-eligible	0.152%	658
European (non-Finnish)	0.0801%	1,249
South Asian	0.0428%	2,335
Admixed American	0.0383%	2,609
African / African-American	0.0267%	3,750
Finnishnot grpmax-eligible	0.00469%	21,333
East Asian	0.00446%	22,439

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: CCT4
Protein: p.Arg483Gln
Coding: c.1448G>A
MANE Select: NM_006430
dbSNP: rs146765948
Type: single nucleotide variant
Location: chr2:61872125 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 90.05 · 72 PDB
Residue 483: an α-helix

Full CCT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT4 p.Arg483Gly Uncertain significance ★ ⚠ same residue
CCT4 p.Ala113Gly Uncertain significance ★ ⚠ same type
CCT4 p.Ala113Val Uncertain significance ★ ⚠ same type
CCT4 p.Ala308Val Uncertain significance ★ ⚠ same type
CCT4 p.Ala408Ser Uncertain significance ★ ⚠ same type
CCT4 p.Ala41Thr Uncertain significance ★ ⚠ same type
CCT4 p.Ala518Ser Uncertain significance ★ ⚠ same type
CCT4 p.Arg274Gln 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/cct4-p-arg483gln (accessed [today's date]).

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