Is CCT7 p.Val23Met (c.67G>A) pathogenic?

CCT7 p.Val23Met (c.67G>A) is classified Uncertain significance in CCT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.2504); Very rare (popmax 0.00167%, amr).

How common is CCT7 p.Val23Met (c.67G>A) in the general population?

CCT7 p.Val23Met (c.67G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CCT7 p.Val23Met (c.67G>A)?

AlphaMissense predicts likely benign (score 0.2504) — an in-silico prediction, not a clinical call.

CCT7 p.Val23Met

c.67G>A · VCV4828636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2504 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2504	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -7.85	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 12	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 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 · 1/60,008 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,870 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,008
European (non-Finnish)	0.000254%	393,284

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.Val23Met
Coding: c.67G>A
MANE Select: NM_006429
Type: single nucleotide variant
Location: chr2:73239703 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.03 · 70 PDB
Residue 23: an α-helix

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-val23met (accessed [today's date]).

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