Is CCNA1 p.Ser64Pro (c.190T>C) pathogenic?

CCNA1 p.Ser64Pro (c.190T>C) is classified Uncertain significance in CCNA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.0713); Absent from gnomAD v4.1.

How common is CCNA1 p.Ser64Pro (c.190T>C) in the general population?

CCNA1 p.Ser64Pro (c.190T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNA1 p.Ser64Pro (c.190T>C)?

AlphaMissense predicts likely benign (score 0.0713) — an in-silico prediction, not a clinical call.

CCNA1 p.Ser64Pro

c.190T>C · VCV3997578

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0713 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0713	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -6.41	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 2.4	GERP -2.3, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 4,512 bp · p 0.00074 · regional, not allelic
Overall
CADD	17.32	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S108P vs ClinVar S64P) — verify the residue.

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: CCNA1
Protein: p.Ser64Pro
Coding: c.190T>C
MANE Select: NM_001413923
Type: single nucleotide variant
Location: chr13:36437653 (GRCh38)
Gene constraint: LOEUF 0.583 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 68.65

Full CCNA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNA1 c.412+5C>A Benign ★★ same type
CCNA1 p.Leu342= Benign ★★ same type
CCNA1 p.Thr196= Benign ★★ same type
CCNA1 p.Tyr63= Benign ★★ same type
CCNA1 c.-101C>G Uncertain significance ★ ⚠ same type
CCNA1 c.-19G>C Uncertain significance ★ ⚠ same type
CCNA1 c.-50C>T Uncertain significance ★ ⚠ same type
CCNA1 c.-51C>A 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/ccna1-p-ser64pro (accessed [today's date]).

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