Is CCT3 p.Gln12Arg (c.35A>G) pathogenic?

CCT3 p.Gln12Arg (c.35A>G) is classified Uncertain significance in CCT3 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-10-04). AlphaMissense: likely benign (0.3126); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with speech or visual impairment and brain hypomyelination.

How common is CCT3 p.Gln12Arg (c.35A>G) in the general population?

CCT3 p.Gln12Arg (c.35A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCT3 p.Gln12Arg (c.35A>G)?

AlphaMissense predicts likely benign (score 0.3126) — an in-silico prediction, not a clinical call.

CCT3 p.Gln12Arg

Q: What condition is associated with CCT3 p.Gln12Arg (c.35A>G)?

CCT3 p.Gln12Arg (c.35A>G) is associated with neurodevelopmental disorder with speech or visual impairment and brain hypomyelination (ClinVar).

c.35A>G · rs2525300756 · VCV2316841

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3126 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder with speech or visual impairment and brain hypomyelination

Computational evidence

Protein change
AlphaMissense	0.3126	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -8.79	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 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 29 kb · p 0.0019 · regional, not allelic
Overall
CADD	24.0	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

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: CCT3
Protein: p.Gln12Arg
Coding: c.35A>G
MANE Select: NM_005998
dbSNP: rs2525300756
Type: single nucleotide variant
Location: chr1:156335885 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.23 · 72 PDB
Residue 12: the 'disordered' region; a UniProt-annotated variant site (in nedsvh; uncertain significance; the orthologous mutation in c. elegans results in reduced worm motility and a crawling speed defect suggesting a deleterious effect on function); a β-strand

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

Disease context

neurodevelopmental disorder with speech or visual impairment and brain hypomyelination — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCT3 p.Arg334Ter Uncertain significance ★ same condition
CCT3 p.Arg518Ter Uncertain significance ★ same condition
CCT3 p.Thr265fs Pathogenic ★ same condition
CCT3 p.Met133fs Uncertain significance ★ same condition
CCT3 p.Gln396fs Pathogenic same condition
CCT3 p.Ala307Thr Uncertain significance ★ ⚠ same type
CCT3 p.Ala421Gly Uncertain significance ★ ⚠ same type
CCT3 p.Ala457Ser 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-gln12arg (accessed [today's date]).

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