Is BMPER p.Cys599Ser (c.1795T>A) pathogenic?

BMPER p.Cys599Ser (c.1795T>A) is classified Uncertain significance in BMPER (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely pathogenic (0.9951); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BMPER p.Cys599Ser (c.1795T>A)?

BMPER p.Cys599Ser (c.1795T>A) is associated with Inborn genetic diseases (ClinVar).

How common is BMPER p.Cys599Ser (c.1795T>A) in the general population?

BMPER p.Cys599Ser (c.1795T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMPER p.Cys599Ser (c.1795T>A)?

AlphaMissense predicts likely pathogenic (score 0.9951) — an in-silico prediction, not a clinical call.

BMPER p.Cys599Ser

c.1795T>A · VCV3992001

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9951	likely pathogenic · top 4% in BMPER
REVEL	0.973	strongly pathogenic-leaning
SaProt	LLR -13.79	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMPER
Protein: p.Cys599Ser
Coding: c.1795T>A
MANE Select: NM_001365308
Type: single nucleotide variant
Location: chr7:34143279 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24

Full BMPER 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

BMPER p.Cys599Trp Uncertain significance ★ ⚠ same residue
BMPER p.Cys599= Benign/Likely benign ★★ same residue
BMPER p.Ala39Ser Uncertain significance ★★ ⚠ same condition
BMPER p.Arg16Ser Uncertain significance ★★ ⚠ same condition
BMPER p.Arg332His Uncertain significance ★★ ⚠ same condition
BMPER p.Arg410His Uncertain significance ★★ ⚠ same condition
BMPER p.Arg505His Uncertain significance ★★ ⚠ same condition
BMPER p.Arg558Gln 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/bmper-p-cys599ser (accessed [today's date]).

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