Is BMPER p.Asn65Lys (c.195C>A) pathogenic?

BMPER p.Asn65Lys (c.195C>A) is classified Uncertain significance in BMPER (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-18). AlphaMissense: likely pathogenic (0.9248); Very rare (popmax 0.0017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BMPER p.Asn65Lys (c.195C>A)?

BMPER p.Asn65Lys (c.195C>A) is associated with Inborn genetic diseases (ClinVar).

How common is BMPER p.Asn65Lys (c.195C>A) in the general population?

BMPER p.Asn65Lys (c.195C>A) is very rare (popmax 0.0017%, nfe) (gnomAD).

What do computational predictors say about BMPER p.Asn65Lys (c.195C>A)?

AlphaMissense predicts likely pathogenic (score 0.9248) — an in-silico prediction, not a clinical call.

BMPER p.Asn65Lys

c.195C>A · rs1236390436 · VCV3134588

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9248 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9248	likely pathogenic
REVEL	0.305	indeterminate
SaProt	LLR -9.64	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.39	GERP -0.27, phastCons 0.077
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	22.2	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 0.0017% European (non-Finnish) · 20/1,179,708 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00124% 20/1,613,504 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: BMPER
Protein: p.Asn65Lys
Coding: c.195C>A
MANE Select: NM_001365308
dbSNP: rs1236390436
Type: single nucleotide variant
Location: chr7:33906879 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 65: the vwfc 1 domain

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.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
BMPER p.Arg582Gln Uncertain significance ★★ ⚠ same condition
BMPER p.Cys394Tyr 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-asn65lys (accessed [today's date]).

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