Is CCT7 p.Leu293Val (c.877C>G) pathogenic?

CCT7 p.Leu293Val (c.877C>G) is classified Uncertain significance in CCT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely pathogenic (0.7713); Ultra-rare (popmax 0.0134%, eas).

How common is CCT7 p.Leu293Val (c.877C>G) in the general population?

CCT7 p.Leu293Val (c.877C>G) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CCT7 p.Leu293Val (c.877C>G)?

AlphaMissense predicts likely pathogenic (score 0.7713) — an in-silico prediction, not a clinical call.

CCT7 p.Leu293Val

c.877C>G · rs768960644 · VCV2547985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7713 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7713	likely pathogenic
REVEL	0.636	indeterminate
SaProt	LLR -14.31	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 15 kb · p 1.7e-05 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0134% East Asian · 6/44,892 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000372% 6/1,614,010 alleles · ultra-rare

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.Leu293Val
Coding: c.877C>G
MANE Select: NM_006429
dbSNP: rs768960644
Type: single nucleotide variant
Location: chr2:73249084 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.03 · 70 PDB
Residue 293: a β-strand

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-leu293val (accessed [today's date]).

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