Is CCT8 p.Arg44His (c.131G>A) pathogenic?

CCT8 p.Arg44His (c.131G>A) is classified Uncertain significance in CCT8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: likely benign (0.2694); Very rare (popmax 0.0067%, eas).

How common is CCT8 p.Arg44His (c.131G>A) in the general population?

CCT8 p.Arg44His (c.131G>A) is very rare (popmax 0.0067%, eas) (gnomAD).

What do computational predictors say about CCT8 p.Arg44His (c.131G>A)?

AlphaMissense predicts likely benign (score 0.2694) — an in-silico prediction, not a clinical call.

CCT8 p.Arg44His

c.131G>A · rs369540224 · VCV2229462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2694	likely benign
REVEL	0.84	moderately pathogenic-leaning
SaProt	LLR -12.60	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 17 kb · p 9.2e-05 · regional, not allelic
Overall
CADD	33.0	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 0.0067% East Asian · 3/44,784 alleles

Filtering AF 0.00287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00196%

Overall 0.00125% 20/1,606,198 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0067%	14,928
South Asian	0.00661%	15,129
African / African-American	0.00268%	37,349
European (non-Finnish)	0.000767%	130,401

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: CCT8
Protein: p.Arg44His
Coding: c.131G>A
MANE Select: NM_006585
dbSNP: rs369540224
Type: single nucleotide variant
Location: chr21:29070267 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 71 PDB
Residue 44: an α-helix

Full CCT8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT8 p.Val409Ile Benign ★★ same type
CCT8 p.Ala12Thr Uncertain significance ★ ⚠ same type
CCT8 p.Ala186Thr Uncertain significance ★ ⚠ same type
CCT8 p.Ala298Thr Uncertain significance ★ ⚠ same type
CCT8 p.Ala35Thr Uncertain significance ★ ⚠ same type
CCT8 p.Ala442Gly Uncertain significance ★ ⚠ same type
CCT8 p.Ala447Val Uncertain significance ★ ⚠ same type
CCT8 p.Ala451Thr 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/cct8-p-arg44his (accessed [today's date]).

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