Is CCT8 p.Ser194= (c.582C>T) pathogenic?

CCT8 p.Ser194= (c.582C>T) is classified Likely benign in CCT8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). Very rare (popmax 0.00403%, afr).

How common is CCT8 p.Ser194= (c.582C>T) in the general population?

CCT8 p.Ser194= (c.582C>T) is very rare (popmax 0.00403%, afr) (gnomAD).

CCT8 p.Ser194=

c.582C>T · VCV4650330

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00403%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.361	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.93 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.3	GERP -3.7
Overall
CADD	4.413	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00403% African / African-American · 3/74,412 alleles

Filtering AF 0.00115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000973%

Overall 0.00193% 31/1,605,984 alleles · very rare exomes 29/1,454,368 · genomes 2/151,616 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00643%	15,544
African / African-Americangrpmax	0.00403%	24,804
East Asian	0.00224%	44,742
European (non-Finnish)	0.00178%	56,025
Admixed American	0.0017%	58,800
South Asian	0.00112%	89,222

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser194=
Coding: c.582C>T
MANE Select: NM_006585
Type: single nucleotide variant
Location: chr21:29066758 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 71 PDB
Residue 194: 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-ser194 (accessed [today's date]).

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