Is CCT6A p.Val271Phe (c.811G>T) pathogenic?

CCT6A p.Val271Phe (c.811G>T) is classified Uncertain significance in CCT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely pathogenic (0.9228); Very rare (popmax 0.00223%, eas).

How common is CCT6A p.Val271Phe (c.811G>T) in the general population?

CCT6A p.Val271Phe (c.811G>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CCT6A p.Val271Phe (c.811G>T)?

AlphaMissense predicts likely pathogenic (score 0.9228) — an in-silico prediction, not a clinical call.

CCT6A p.Val271Phe

c.811G>T · rs759504485 · VCV3140190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9228 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9228	likely pathogenic
REVEL	0.834	moderately pathogenic-leaning
SaProt	LLR -9.09	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 5,082 bp · p 0.00016 · regional, not allelic
Overall
CADD	24.2	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 0.00223% East Asian · 1/44,812 alleles

Overall 0.000187% 3/1,604,518 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,812
Admixed American	0.00173%	57,946
South Asian	0.00112%	88,942

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: CCT6A
Protein: p.Val271Phe
Coding: c.811G>T
MANE Select: NM_001762
dbSNP: rs759504485
Type: single nucleotide variant
Location: chr7:56058447 (GRCh38)
Gene constraint: LOEUF 0.234 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 71 PDB
Residue 271: an α-helix

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-val271phe (accessed [today's date]).

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