Is CCT3 p.His4Tyr (c.10C>T) pathogenic?

CCT3 p.His4Tyr (c.10C>T) is classified Uncertain significance in CCT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-05). AlphaMissense: likely benign (0.1616); Very rare (popmax 0.00557%, amr).

How common is CCT3 p.His4Tyr (c.10C>T) in the general population?

CCT3 p.His4Tyr (c.10C>T) is very rare (popmax 0.00557%, amr) (gnomAD).

What do computational predictors say about CCT3 p.His4Tyr (c.10C>T)?

AlphaMissense predicts likely benign (score 0.1616) — an in-silico prediction, not a clinical call.

CCT3 p.His4Tyr

c.10C>T · VCV3264671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1616 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00557%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1616	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -7.46	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 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 29 kb · p 0.0019 · regional, not allelic
Overall
CADD	23.0	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 0.00557% Admixed American · 3/53,828 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000441% 7/1,588,438 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00557%	17,943
African / African-American	0.00535%	18,706

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: CCT3
Protein: p.His4Tyr
Coding: c.10C>T
MANE Select: NM_005998
Type: single nucleotide variant
Location: chr1:156338175 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.23 · 72 PDB
Residue 4: the 'disordered' region

Full CCT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT3 p.Ala307Thr Uncertain significance ★ ⚠ same type
CCT3 p.Ala421Gly Uncertain significance ★ ⚠ same type
CCT3 p.Ala457Ser Uncertain significance ★ ⚠ same type
CCT3 p.Arg127Cys Uncertain significance ★ ⚠ same type
CCT3 p.Arg167Gln Uncertain significance ★ ⚠ same type
CCT3 p.Arg16Cys Uncertain significance ★ ⚠ same type
CCT3 p.Arg230Gln Uncertain significance ★ ⚠ same type
CCT3 p.Arg230Trp 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/cct3-p-his4tyr (accessed [today's date]).

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