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

CENPV p.Pro87Ser (c.259C>T) is classified Benign in CENPV (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-17). Ultra-rare (popmax 0.0491%, mid).

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

CENPV p.Pro87Ser (c.259C>T) is ultra-rare (popmax 0.0491%, mid) (gnomAD).

CENPV p.Pro87Ser

c.259C>T · rs201815751 · VCV736394

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0491%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.216	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1.8, phastCons 0.61
Regional constraint	o/e 1.22	unconstrained · MANE · 284 bp · p 0.0082 · regional, not allelic
Overall
CADD	19.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0491% Middle Eastern · 2/4,072 alleles

Filtering AF 0.0146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.0383% 542/1,415,386 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.48%	68
Remaining individualsnot grpmax-eligible	0.116%	865
Middle Easterngrpmax	0.0491%	2,036
Admixed American	0.028%	3,577
European (non-Finnish)	0.0119%	8,438
African / African-American	0.0089%	11,241
Finnishnot grpmax-eligible	0.0022%	45,550

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CENPV
Protein: p.Pro87Ser
Coding: c.259C>T
MANE Select: NM_181716
dbSNP: rs201815751
Type: single nucleotide variant
Location: chr17:16353178 (GRCh38)
Gene constraint: LOEUF 0.953 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 80.30
Residue 87: the 'disordered' region

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

Similar variants

CENPV p.Ala186Pro Uncertain significance ★ same type
CENPV p.Ala25Glu Uncertain significance ★ same type
CENPV p.Ala25Gly Uncertain significance ★ same type
CENPV p.Ala28Ser Uncertain significance ★ same type
CENPV p.Ala28Val Uncertain significance ★ same type
CENPV p.Ala29Gly Uncertain significance ★ same type
CENPV p.Ala31Val Uncertain significance ★ same type
CENPV p.Ala84Thr 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/cenpv-p-pro87ser (accessed [today's date]).

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