Is CCT2 p.Asn426Ser (c.1277A>G) pathogenic?

CCT2 p.Asn426Ser (c.1277A>G) is classified Uncertain significance in CCT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.0565); Ultra-rare (popmax 0.0357%, eas).

How common is CCT2 p.Asn426Ser (c.1277A>G) in the general population?

CCT2 p.Asn426Ser (c.1277A>G) is ultra-rare (popmax 0.0357%, eas) (gnomAD).

What do computational predictors say about CCT2 p.Asn426Ser (c.1277A>G)?

AlphaMissense predicts likely benign (score 0.0565) — an in-silico prediction, not a clinical call.

CCT2 p.Asn426Ser

c.1277A>G · rs558771848 · VCV1419267

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0565 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0565	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -6.44	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 -0.24	GERP -4.6
Regional constraint	o/e 0.90	unconstrained · MANE · 4,143 bp · p 0.12 · regional, not allelic
Overall
CADD	4.899	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 0.0357% East Asian · 16/44,862 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00217% 35/1,614,082 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0357%	2,804
Admixed American	0.00833%	12,003
South Asian	0.00329%	30,358
Remaining individualsnot grpmax-eligible	0.0032%	31,254
Finnishnot grpmax-eligible	0.00312%	32,020
European (non-Finnish)	0.000593%	168,564

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.Asn426Ser
Coding: c.1277A>G
MANE Select: NM_006431
dbSNP: rs558771848
Type: single nucleotide variant
Location: chr12:69598013 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.85 · 71 PDB
Residue 426: an α-helix

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-asn426ser (accessed [today's date]).

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