Is CCT6B p.Val450Phe (c.1348G>T) pathogenic?

CCT6B p.Val450Phe (c.1348G>T) is classified Uncertain significance in CCT6B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: ambiguous (0.4668); Ultra-rare (popmax 0.0259%, eas).

How common is CCT6B p.Val450Phe (c.1348G>T) in the general population?

CCT6B p.Val450Phe (c.1348G>T) is ultra-rare (popmax 0.0259%, eas) (gnomAD).

What do computational predictors say about CCT6B p.Val450Phe (c.1348G>T)?

AlphaMissense predicts ambiguous (score 0.4668) — an in-silico prediction, not a clinical call.

CCT6B p.Val450Phe

c.1348G>T · rs770681410 · VCV2615171

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4668 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0259%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4668	ambiguous
REVEL	0.85	moderately pathogenic-leaning
SaProt	LLR -12.30	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	loss · gain 0.07 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6	GERP 2.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 33 kb · p 0.21 · regional, not allelic
Overall
CADD	33.0	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 0.0259% East Asian · 11/42,546 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00114% 16/1,400,990 alleles · ultra-rare exomes 16/1,249,462 · genomes 0/151,528 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0259%	3,868
Remaining individualsnot grpmax-eligible	0.00186%	53,696
Admixed American	0.0018%	55,498
European (non-Finnish)	0.000294%	339,624

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: CCT6B
Protein: p.Val450Phe
Coding: c.1348G>T
MANE Select: NM_006584
dbSNP: rs770681410
Type: single nucleotide variant
Location: chr17:34931051 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.98

Full CCT6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT6B c.615-2A>G Benign ★★ same type
CCT6B p.Ala126Thr Uncertain significance ★ ⚠ same type
CCT6B p.Ala16Val Uncertain significance ★ ⚠ same type
CCT6B p.Ala18Val Uncertain significance ★ ⚠ same type
CCT6B p.Ala262Pro Uncertain significance ★ ⚠ same type
CCT6B p.Ala2Val Uncertain significance ★ ⚠ same type
CCT6B p.Ala390Asp Uncertain significance ★ ⚠ same type
CCT6B p.Ala433Asp 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/cct6b-p-val450phe (accessed [today's date]).

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