Is CCT8L2 p.Ala151Pro (c.451G>C) pathogenic?

CCT8L2 p.Ala151Pro (c.451G>C) is classified Uncertain significance in CCT8L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: ambiguous (0.4287); Very rare (popmax 0.00891%, eas).

How common is CCT8L2 p.Ala151Pro (c.451G>C) in the general population?

CCT8L2 p.Ala151Pro (c.451G>C) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CCT8L2 p.Ala151Pro (c.451G>C)?

AlphaMissense predicts ambiguous (score 0.4287) — an in-silico prediction, not a clinical call.

CCT8L2 p.Ala151Pro

c.451G>C · VCV3997908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4287 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Computational evidence

Protein change
AlphaMissense	0.4287	ambiguous
REVEL	0.356	indeterminate
SaProt	LLR -11.44	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 1,670 bp · p 5.2e-05 · regional, not allelic
Overall
CADD	21.7	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 0.00891% East Asian · 4/44,870 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000248% 4/1,614,204 alleles · very rare exomes 4/1,461,874 · genomes 0/152,330 · joint denominator

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: CCT8L2
Protein: p.Ala151Pro
Coding: c.451G>C
MANE Select: NM_014406
Type: single nucleotide variant
Location: chr22:16592100 (GRCh38)
Gene constraint: LOEUF 1.252 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.62

Full CCT8L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT8L2 p.Pro344Thr Benign ★★ same type
CCT8L2 p.Ala106Asp Uncertain significance ★ same type
CCT8L2 p.Ala106Gly Uncertain significance ★ ⚠ same type
CCT8L2 p.Ala137Thr Uncertain significance ★ ⚠ same type
CCT8L2 p.Ala141Ser Uncertain significance ★ ⚠ same type
CCT8L2 p.Ala145Thr Uncertain significance ★ ⚠ same type
CCT8L2 p.Ala185Asp Uncertain significance ★ ⚠ same type
CCT8L2 p.Ala190Thr 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/cct8l2-p-ala151pro (accessed [today's date]).

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