Is CCT2 p.Gln124His (c.372G>C) pathogenic?

CCT2 p.Gln124His (c.372G>C) is classified Uncertain significance in CCT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely pathogenic (0.8966); Ultra-rare (popmax 0.02%, amr).

How common is CCT2 p.Gln124His (c.372G>C) in the general population?

CCT2 p.Gln124His (c.372G>C) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about CCT2 p.Gln124His (c.372G>C)?

AlphaMissense predicts likely pathogenic (score 0.8966) — an in-silico prediction, not a clinical call.

CCT2 p.Gln124His

c.372G>C · rs772568145 · VCV1047518

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8966 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8966	likely pathogenic
REVEL	0.576	indeterminate
SaProt	LLR -9.66	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP -3.9, phastCons 0.98
Regional constraint	o/e 0.88	unconstrained · MANE · 7,571 bp · p 0.023 · regional, not allelic
Overall
CADD	21.2	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 0.02% Admixed American · 12/60,024 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.000889% 13/1,461,788 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,002
South Asian	0.0011%	91,072

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.Gln124His
Coding: c.372G>C
MANE Select: NM_006431
dbSNP: rs772568145
Type: single nucleotide variant
Location: chr12:69588188 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.85 · 71 PDB

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-gln124his (accessed [today's date]).

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