Is CCNT2 p.Ser646Asn (c.1937G>A) pathogenic?

CCNT2 p.Ser646Asn (c.1937G>A) is classified Uncertain significance in CCNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.2777); Very rare (popmax 0.000254%, nfe).

How common is CCNT2 p.Ser646Asn (c.1937G>A) in the general population?

CCNT2 p.Ser646Asn (c.1937G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CCNT2 p.Ser646Asn (c.1937G>A)?

AlphaMissense predicts likely benign (score 0.2777) — an in-silico prediction, not a clinical call.

CCNT2 p.Ser646Asn

c.1937G>A · VCV3997715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2777 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2777	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -10.12	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,371 bp · p 0.29 · regional, not allelic
Overall
CADD	22.8	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 0.000254% European (non-Finnish) · 3/1,179,988 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,844 alleles · very rare

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: CCNT2
Protein: p.Ser646Asn
Coding: c.1937G>A
MANE Select: NM_058241
Type: single nucleotide variant
Location: chr2:134954392 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.93 · 1 PDB
Residue 646: the 'disordered' region

Full CCNT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNT2 p.Asp717Asn Uncertain significance ★★ ⚠ same type
CCNT2 p.Ala335Ser Uncertain significance ★ ⚠ same type
CCNT2 p.Ala458Thr Uncertain significance ★ ⚠ same type
CCNT2 p.Arg255Gln Uncertain significance ★ ⚠ same type
CCNT2 p.Arg255Ter Uncertain significance ★ same type
CCNT2 p.Asn208Asp Uncertain significance ★ ⚠ same type
CCNT2 p.Asn700Ser Uncertain significance ★ ⚠ same type
CCNT2 p.Asn729Ser 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/ccnt2-p-ser646asn (accessed [today's date]).

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