Is CCNA1 p.Pro87Ser (c.259C>T) pathogenic?

CCNA1 p.Pro87Ser (c.259C>T) is classified Uncertain significance in CCNA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.0706); Very rare (popmax 0.0011%, sas).

How common is CCNA1 p.Pro87Ser (c.259C>T) in the general population?

CCNA1 p.Pro87Ser (c.259C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CCNA1 p.Pro87Ser (c.259C>T)?

AlphaMissense predicts likely benign (score 0.0706) — an in-silico prediction, not a clinical call.

CCNA1 p.Pro87Ser

c.259C>T · rs2500419929 · VCV2243542

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0706 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0706	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.84	GERP -1.7, phastCons 0.008
Regional constraint	o/e 1.11	unconstrained · MANE · 426 bp · p 0.29 · regional, not allelic
Overall
CADD	2.513	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 P131S vs ClinVar P87S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,086 alleles

Overall 6.2e-05% 1/1,614,120 alleles · very rare exomes 1/1,461,868 · genomes 0/152,252 · 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: CCNA1
Protein: p.Pro87Ser
Coding: c.259C>T
MANE Select: NM_001413923
dbSNP: rs2500419929
Type: single nucleotide variant
Location: chr13:36437722 (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-pro87ser (accessed [today's date]).

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