Is CCT2 p.Asp151Asn (c.451G>A) pathogenic?

CCT2 p.Asp151Asn (c.451G>A) is classified Uncertain significance in CCT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). AlphaMissense: likely benign (0.088); Ultra-rare (popmax 0.0164%, mid).

How common is CCT2 p.Asp151Asn (c.451G>A) in the general population?

CCT2 p.Asp151Asn (c.451G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CCT2 p.Asp151Asn (c.451G>A)?

AlphaMissense predicts likely benign (score 0.088) — an in-silico prediction, not a clinical call.

CCT2 p.Asp151Asn

c.451G>A · rs368079574 · VCV2413802

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.088 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.088	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -8.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 7,571 bp · p 0.023 · regional, not allelic
Overall
CADD	22.1	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

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.0106% 171/1,613,252 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
European (non-Finnish)	0.0136%	7,371
African / African-American	0.00534%	18,722
Admixed American	0.00333%	29,997
Remaining individualsnot grpmax-eligible	0.0032%	31,232
South Asian	0.0022%	45,529

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.Asp151Asn
Coding: c.451G>A
MANE Select: NM_006431
dbSNP: rs368079574
Type: single nucleotide variant
Location: chr12:69589489 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.85 · 71 PDB
Residue 151: a β-strand

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

Similar variants

CCT2 p.Asp151= Likely benign ★ same residue
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

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-asp151asn (accessed [today's date]).

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