Is CPE p.Arg262Trp (c.784C>T) pathogenic?

CPE p.Arg262Trp (c.784C>T) is classified Uncertain significance in CPE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-08). AlphaMissense: ambiguous (0.446); Ultra-rare (popmax 0.0307%, afr); Associated with Inborn genetic diseases.

What condition is associated with CPE p.Arg262Trp (c.784C>T)?

CPE p.Arg262Trp (c.784C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CPE p.Arg262Trp (c.784C>T) in the general population?

CPE p.Arg262Trp (c.784C>T) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

What do computational predictors say about CPE p.Arg262Trp (c.784C>T)?

AlphaMissense predicts ambiguous (score 0.446) — an in-silico prediction, not a clinical call.

CPE p.Arg262Trp

c.784C>T · rs376055726 · VCV2160231

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.446 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.446	ambiguous
REVEL	0.319	indeterminate
SaProt	LLR -14.36	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.42	GERP -1.2, phastCons 0.025
Regional constraint	o/e 0.85	unconstrained · MANE · 118 kb · p 0.00025 · regional, not allelic
Overall
CADD	21.2	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 0.0307% African / African-American · 23/74,834 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00318% 51/1,604,586 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,254
Remaining individualsnot grpmax-eligible	0.00965%	10,361
East Asian	0.00446%	22,397
South Asian	0.0022%	45,417
Admixed American	0.00167%	59,974
Finnishnot grpmax-eligible	0.00156%	64,026
European (non-Finnish)	0.00137%	73,218

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: CPE
Protein: p.Arg262Trp
Coding: c.784C>T
MANE Select: NM_001873
dbSNP: rs376055726
Type: single nucleotide variant
Location: chr4:165482353 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 90.83
Residue 262: a UniProt-annotated variant site (in bdvs); the peptidase m14 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPE p.Arg262Gln Uncertain significance ★ ⚠ same residue
CPE p.Arg297Trp Uncertain significance ★★ ⚠ same condition
CPE p.Asp251Gly Uncertain significance ★★ ⚠ same condition
CPE p.Asp304Ala Uncertain significance ★★ ⚠ same condition
CPE p.Trp21Cys Uncertain significance ★★ ⚠ same condition
CPE p.Gln384= Likely benign ★★ same condition
CPE p.Gln384Ter Pathogenic ★ same condition
CPE p.Ala166Thr Uncertain significance ★ ⚠ same condition

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/cpe-p-arg262trp (accessed [today's date]).

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