Is BMPER p.Arg16Ser (c.46C>A) pathogenic?

BMPER p.Arg16Ser (c.46C>A) is classified Uncertain significance in BMPER (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-16). AlphaMissense: likely benign (0.1721); Ultra-rare (popmax 0.0468%, eas); Associated with Inborn genetic diseases.

What condition is associated with BMPER p.Arg16Ser (c.46C>A)?

BMPER p.Arg16Ser (c.46C>A) is associated with Inborn genetic diseases (ClinVar).

How common is BMPER p.Arg16Ser (c.46C>A) in the general population?

BMPER p.Arg16Ser (c.46C>A) is ultra-rare (popmax 0.0468%, eas) (gnomAD).

What do computational predictors say about BMPER p.Arg16Ser (c.46C>A)?

AlphaMissense predicts likely benign (score 0.1721) — an in-silico prediction, not a clinical call.

BMPER p.Arg16Ser

c.46C>A · rs760953708 · VCV1429321

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1721 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0468%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1721	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 0.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	18.77	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.0468% East Asian · 21/44,850 alleles

Filtering AF 0.0313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0263%

Overall 0.00155% 25/1,613,324 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0468%	2,136
Remaining individualsnot grpmax-eligible	0.0032%	31,234
African / African-American	0.00267%	37,431

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.Arg16Ser
Coding: c.46C>A
MANE Select: NM_001365308
dbSNP: rs760953708
Type: single nucleotide variant
Location: chr7:33905659 (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.Arg16Leu Uncertain significance ★ ⚠ same residue
BMPER p.Ala39Ser 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.Asn65Lys 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-arg16ser (accessed [today's date]).

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