Is CENPP p.His62Arg (c.185A>G) pathogenic?

CENPP p.His62Arg (c.185A>G) is classified Uncertain significance in CENPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: likely benign (0.0919); Ultra-rare (popmax 0.0112%, eas).

How common is CENPP p.His62Arg (c.185A>G) in the general population?

CENPP p.His62Arg (c.185A>G) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about CENPP p.His62Arg (c.185A>G)?

AlphaMissense predicts likely benign (score 0.0919) — an in-silico prediction, not a clinical call.

CENPP p.His62Arg

c.185A>G · VCV4225733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0919 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0919	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -5.53	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 1.5	GERP -1.4, phastCons 0.003
Regional constraint	o/e 0.96	unconstrained · MANE · 287 kb · p 0.47 · regional, not allelic
Overall
CADD	10.98	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% East Asian · 5/44,794 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00124% 20/1,613,214 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,959
Remaining individualsnot grpmax-eligible	0.0032%	31,223
Admixed American	0.00167%	59,918
European (non-Finnish)	0.00102%	98,298

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.His62Arg
Coding: c.185A>G
MANE Select: NM_001012267
Type: single nucleotide variant
Location: chr9:92332247 (GRCh38)
Gene constraint: LOEUF 1.272 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.96 · 13 PDB
Residue 62: an α-helix

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

Similar variants

ECM2 p.Thr62Ile Uncertain significance ★ ⚠ same residue
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

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-his62arg (accessed [today's date]).

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