Is CCT3 p.Val144Asp (c.431T>A) pathogenic?

CCT3 p.Val144Asp (c.431T>A) is classified Uncertain significance in CCT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely pathogenic (0.9446); Absent from gnomAD v4.1.

How common is CCT3 p.Val144Asp (c.431T>A) in the general population?

CCT3 p.Val144Asp (c.431T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCT3 p.Val144Asp (c.431T>A)?

AlphaMissense predicts likely pathogenic (score 0.9446) — an in-silico prediction, not a clinical call.

CCT3 p.Val144Asp

c.431T>A · VCV4222384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9446 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9446	likely pathogenic
REVEL	0.801	moderately pathogenic-leaning
SaProt	LLR -14.68	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 29 kb · p 0.0019 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Val144Asp
Coding: c.431T>A
MANE Select: NM_005998
Type: single nucleotide variant
Location: chr1:156321017 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.23 · 72 PDB

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-val144asp (accessed [today's date]).

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