Is CENPE p.Arg1597Ser (c.4791A>C) pathogenic?

CENPE p.Arg1597Ser (c.4791A>C) is classified Conflicting classifications of pathogenicity in CENPE (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.2507); Rare (popmax 0.651%, nfe).

How common is CENPE p.Arg1597Ser (c.4791A>C) in the general population?

CENPE p.Arg1597Ser (c.4791A>C) is rare (popmax 0.651%, nfe) (gnomAD).

What do computational predictors say about CENPE p.Arg1597Ser (c.4791A>C)?

AlphaMissense predicts likely benign (score 0.2507) — an in-silico prediction, not a clinical call.

CENPE p.Arg1597Ser

c.4791A>C · rs61751594 · VCV434695

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2507 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.651%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.2507	likely benign
REVEL	0.23	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.6	GERP -4
Regional constraint	o/e 0.97	unconstrained · MANE · 71 kb · p 0.13 · regional, not allelic
Overall
CADD	5.032	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 0.651% European (non-Finnish) · 7,676/1,178,798 alleles

Filtering AF 0.639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.634%

Overall 0.528% 8,508/1,611,142 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.651%	154
Remaining individualsnot grpmax-eligible	0.476%	210
Admixed American	0.389%	257
Ashkenazi Jewishnot grpmax-eligible	0.261%	383
Middle Eastern	0.231%	432
African / African-American	0.106%	947
Finnishnot grpmax-eligible	0.0909%	1,100
South Asian	0.0796%	1,256
East Asian	0.0067%	14,935

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: CENPE
Protein: p.Arg1597Ser
Coding: c.4791A>C
MANE Select: NM_001813
dbSNP: rs61751594
Type: single nucleotide variant
Location: chr4:103145116 (GRCh38)
Gene constraint: LOEUF 0.451 · pLI 1.00 (gnomAD)

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

Similar variants

CENPE p.Arg1597= Likely benign ★ same residue
CENPE p.Arg2279Cys Uncertain significance ★★ ⚠ same type
CENPE p.Arg760Ser Uncertain significance ★★ ⚠ same type
CENPE p.Asn1145Lys Uncertain significance ★★ ⚠ same type
CENPE p.Asn1165Ser Uncertain significance ★★ ⚠ same type
CENPE p.Asp1960Tyr Uncertain significance ★★ ⚠ same type
CENPE p.Asp954Asn Uncertain significance ★★ same type
CENPE p.Asp954Tyr 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/cenpe-p-arg1597ser (accessed [today's date]).

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