Is CCT6A p.Leu206Phe (c.618A>C) pathogenic?

CCT6A p.Leu206Phe (c.618A>C) is classified Uncertain significance in CCT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-29). AlphaMissense: ambiguous (0.3445); Absent from gnomAD v4.1.

How common is CCT6A p.Leu206Phe (c.618A>C) in the general population?

CCT6A p.Leu206Phe (c.618A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCT6A p.Leu206Phe (c.618A>C)?

AlphaMissense predicts ambiguous (score 0.3445) — an in-silico prediction, not a clinical call.

CCT6A p.Leu206Phe

c.618A>C · VCV3829285

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3445 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3445	ambiguous
REVEL	0.699	pathogenic-leaning
SaProt	LLR -10.71	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	phastCons 0.98
Regional constraint	o/e 1.13	unconstrained · MANE · 2,272 bp · p 0.24 · regional, not allelic
Overall
CADD	18.15	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCT6A
Protein: p.Leu206Phe
Coding: c.618A>C
MANE Select: NM_001762
Type: single nucleotide variant
Location: chr7:56057996 (GRCh38)
Gene constraint: LOEUF 0.234 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 71 PDB
Residue 206: a β-strand

Full CCT6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT6A p.Ser473= Benign ★★ same type
CCT6A c.1450+1G>A Uncertain significance ★ same type
CCT6A p.Ala14Val Uncertain significance ★ ⚠ same type
CCT6A p.Ala253Val Uncertain significance ★ same type
CCT6A p.Ala2Pro Uncertain significance ★ ⚠ same type
CCT6A p.Ala401Gly Uncertain significance ★ ⚠ same type
CCT6A p.Ala452Ser Uncertain significance ★ ⚠ same type
CCT6A p.Ala452Val 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/cct6a-p-leu206phe (accessed [today's date]).

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