Is CCT7 p.Lys366Glu (c.1096A>G) pathogenic?

CCT7 p.Lys366Glu (c.1096A>G) is classified Uncertain significance in CCT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1023); Very rare (popmax 0.00167%, amr).

How common is CCT7 p.Lys366Glu (c.1096A>G) in the general population?

CCT7 p.Lys366Glu (c.1096A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CCT7 p.Lys366Glu (c.1096A>G)?

AlphaMissense predicts likely benign (score 0.1023) — an in-silico prediction, not a clinical call.

CCT7 p.Lys366Glu

c.1096A>G · rs1208548060 · VCV3140199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1023 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1023	likely benign
REVEL	0.372	indeterminate
SaProt	LLR -5.70	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.24	acceptor loss, 3 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 9.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 3,687 bp · p 0.00024 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00167% Admixed American · 1/59,992 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,613,998 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,992
African / African-American	0.00134%	74,894
European (non-Finnish)	0.000424%	236,008

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: CCT7
Protein: p.Lys366Glu
Coding: c.1096A>G
MANE Select: NM_006429
dbSNP: rs1208548060
Type: single nucleotide variant
Location: chr2:73250331 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.03 · 70 PDB

Full CCT7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT7 p.Ala101Thr Uncertain significance ★ ⚠ same type
CCT7 p.Ala182Thr Uncertain significance ★ ⚠ same type
CCT7 p.Ala299Gly Uncertain significance ★ ⚠ same type
CCT7 p.Ala502Val Uncertain significance ★ ⚠ same type
CCT7 p.Ala506Val Uncertain significance ★ ⚠ same type
CCT7 p.Ala510Val Uncertain significance ★ ⚠ same type
CCT7 p.Arg126Cys Uncertain significance ★ ⚠ same type
CCT7 p.Arg344Gln 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/cct7-p-lys366glu (accessed [today's date]).

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