Is CCT6B p.Asp166Val (c.497A>T) pathogenic?

CCT6B p.Asp166Val (c.497A>T) is classified Uncertain significance in CCT6B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). AlphaMissense: likely benign (0.1594); Very rare (popmax 0.0069%, amr).

How common is CCT6B p.Asp166Val (c.497A>T) in the general population?

CCT6B p.Asp166Val (c.497A>T) is very rare (popmax 0.0069%, amr) (gnomAD).

What do computational predictors say about CCT6B p.Asp166Val (c.497A>T)?

AlphaMissense predicts likely benign (score 0.1594) — an in-silico prediction, not a clinical call.

CCT6B p.Asp166Val

c.497A>T · VCV3264680

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1594 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0069%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1594	likely benign
REVEL	0.67	pathogenic-leaning
SaProt	LLR -9.62	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.77, phastCons 0.062
Regional constraint	o/e 1.05	unconstrained · MANE · 33 kb · p 0.21 · regional, not allelic
Overall
CADD	22.3	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 0.0069% Admixed American · 4/57,980 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.000561% 9/1,605,388 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0069%	14,495
African / African-American	0.00404%	24,767
Remaining individualsnot grpmax-eligible	0.00322%	31,062

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.Asp166Val
Coding: c.497A>T
MANE Select: NM_006584
Type: single nucleotide variant
Location: chr17:34954439 (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-asp166val (accessed [today's date]).

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