Is CCT8 p.Val291Ile (c.871G>A) pathogenic?

CCT8 p.Val291Ile (c.871G>A) is classified Likely benign in CCT8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-16). AlphaMissense: likely benign (0.0741); Very rare (popmax 0.00659%, sas).

How common is CCT8 p.Val291Ile (c.871G>A) in the general population?

CCT8 p.Val291Ile (c.871G>A) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about CCT8 p.Val291Ile (c.871G>A)?

AlphaMissense predicts likely benign (score 0.0741) — an in-silico prediction, not a clinical call.

CCT8 p.Val291Ile

c.871G>A · VCV3264685

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0741 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0741	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -4.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.81	GERP -3.7
Regional constraint	o/e 0.85	unconstrained · MANE · 17 kb · p 9.2e-05 · regional, not allelic
Overall
CADD	11.89	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 0.00659% South Asian · 6/91,076 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00434% 70/1,613,970 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,179
European (non-Finnish)	0.00483%	20,700
African / African-American	0.004%	25,011
Admixed American	0.00333%	30,009
Remaining individualsnot grpmax-eligible	0.0032%	31,248

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.Val291Ile
Coding: c.871G>A
MANE Select: NM_006585
Type: single nucleotide variant
Location: chr21:29063422 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 71 PDB
Residue 291: a β-strand

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-val291ile (accessed [today's date]).

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