Is CPE p.Arg121Ter (c.361C>T) pathogenic?

CPE p.Arg121Ter (c.361C>T) is classified Pathogenic in CPE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-29). Very rare (popmax 0.000137%); Associated with Blakemore-Durmaz-Vasileiou (BDV) syndrome.

What condition is associated with CPE p.Arg121Ter (c.361C>T)?

CPE p.Arg121Ter (c.361C>T) is associated with Blakemore-Durmaz-Vasileiou (BDV) syndrome, BDV syndrome (ClinVar).

How common is CPE p.Arg121Ter (c.361C>T) in the general population?

CPE p.Arg121Ter (c.361C>T) is very rare (popmax 0.000137%) (gnomAD).

CPE p.Arg121Ter

c.361C>T · rs1317332155 · VCV1209851

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000137%)

Conditions

Blakemore-Durmaz-Vasileiou (BDV) syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 9
Splicing
SpliceAI	Δ0.24	acceptor gain · deltas
Pangolin	Δ0.33	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.7	GERP 0.18, phastCons 0.99
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000137%

Overall 0.000137% 2/1,461,064 alleles · very rare

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.Arg121Ter
Coding: c.361C>T
MANE Select: NM_001873
dbSNP: rs1317332155
Type: single nucleotide variant
Location: chr4:165464443 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 90.83
Residue 121: 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

Blakemore-Durmaz-Vasileiou (BDV) syndrome

Also linked: BDV syndrome

Similar variants

CPE p.Arg121Gln Uncertain significance ⚠ same residue
CPE p.Leu474= Benign/Likely benign ★★ same condition
CPE c.974-3C>T Uncertain significance ★ same condition
CPE p.Ile415Met Uncertain significance ★ ⚠ same condition
CPE p.Pro30Ala Uncertain significance ★ ⚠ same condition
CPE p.Tyr135Ter Pathogenic same condition
CPE c.673-2A>G Uncertain significance same condition
CPE p.Ala231Gly 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-arg121ter (accessed [today's date]).

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