Is CENPP p.Ser210Arg (c.630C>A) pathogenic?

CENPP p.Ser210Arg (c.630C>A) is classified Uncertain significance in CENPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely pathogenic (0.6938); Ultra-rare (popmax 0.0231%, nfe).

How common is CENPP p.Ser210Arg (c.630C>A) in the general population?

CENPP p.Ser210Arg (c.630C>A) is ultra-rare (popmax 0.0231%, nfe) (gnomAD).

What do computational predictors say about CENPP p.Ser210Arg (c.630C>A)?

AlphaMissense predicts likely pathogenic (score 0.6938) — an in-silico prediction, not a clinical call.

CENPP p.Ser210Arg

c.630C>A · rs138631718 · VCV2517113

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6938 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6938	likely pathogenic · top 10% in CENPP
REVEL	0.077	moderately benign-leaning
SaProt	LLR -8.75	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3	GERP -4.3
Regional constraint	o/e 0.96	unconstrained · MANE · 287 kb · p 0.47 · regional, not allelic
Overall
CADD	0.612	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 0.0231% European (non-Finnish) · 272/1,179,906 alleles

Filtering AF 0.0208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0199%

Overall 0.0174% 281/1,612,918 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0231%	4,338
African / African-American	0.00667%	14,982
Remaining individualsnot grpmax-eligible	0.00481%	20,810
South Asian	0.0011%	91,018

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: CENPP
Protein: p.Ser210Arg
Coding: c.630C>A
MANE Select: NM_001012267
dbSNP: rs138631718
Type: single nucleotide variant
Location: chr9:92611379 (GRCh38)
Gene constraint: LOEUF 1.272 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.96 · 13 PDB

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

Similar variants

CENPP p.Cys283Ter Likely pathogenic ★ same type
CENPP p.Ala17Val Uncertain significance ★ ⚠ same type
CENPP p.Ala211Thr Uncertain significance ★ ⚠ same type
CENPP p.Ala258Gly Uncertain significance ★ ⚠ same type
CENPP p.Arg180His Uncertain significance ★ ⚠ same type
CENPP p.Arg209Cys Uncertain significance ★ ⚠ same type
CENPP p.Arg209Gly Uncertain significance ★ ⚠ same type
CENPP p.Arg209His 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/cenpp-p-ser210arg (accessed [today's date]).

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