Is CCT2 p.Ala34Thr (c.100G>A) pathogenic?

CCT2 p.Ala34Thr (c.100G>A) is classified Uncertain significance in CCT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-30). AlphaMissense: ambiguous (0.3429); Very rare (popmax 0.00872%, amr).

How common is CCT2 p.Ala34Thr (c.100G>A) in the general population?

CCT2 p.Ala34Thr (c.100G>A) is very rare (popmax 0.00872%, amr) (gnomAD).

What do computational predictors say about CCT2 p.Ala34Thr (c.100G>A)?

AlphaMissense predicts ambiguous (score 0.3429) — an in-silico prediction, not a clinical call.

CCT2 p.Ala34Thr

c.100G>A · rs747763186 · VCV1504679

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3429 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00872%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3429	ambiguous
REVEL	0.253	benign-leaning
SaProt	LLR -7.31	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 7,571 bp · p 0.023 · regional, not allelic
Overall
CADD	30.0	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 0.00872% Admixed American · 5/57,324 alleles

Filtering AF 0.00338% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00215%

Overall 0.00106% 17/1,600,170 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00872%	11,465
European (non-Finnish)	0.00102%	97,917

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: CCT2
Protein: p.Ala34Thr
Coding: c.100G>A
MANE Select: NM_006431
dbSNP: rs747763186
Type: single nucleotide variant
Location: chr12:69586774 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.85 · 71 PDB
Residue 34: an α-helix

Full CCT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT2 p.Ala128Thr Uncertain significance ★★ ⚠ same type
CCT2 p.Ala133Val Uncertain significance ★★ ⚠ same type
CCT2 p.Ala145Val Uncertain significance ★★ ⚠ same type
CCT2 p.Arg156Cys Uncertain significance ★★ ⚠ same type
CCT2 p.Arg255Gln Uncertain significance ★★ ⚠ same type
CCT2 p.Arg255Trp Uncertain significance ★★ ⚠ same type
CCT2 p.Arg281Cys Uncertain significance ★★ ⚠ same type
CCT2 p.Arg281His 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/cct2-p-ala34thr (accessed [today's date]).

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