Is BMPER p.Pro124Leu (c.371C>T) pathogenic?

BMPER p.Pro124Leu (c.371C>T) is classified Uncertain significance in BMPER (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). AlphaMissense: likely benign (0.0634); Very rare (popmax 0.00769%, sas).

How common is BMPER p.Pro124Leu (c.371C>T) in the general population?

BMPER p.Pro124Leu (c.371C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about BMPER p.Pro124Leu (c.371C>T)?

AlphaMissense predicts likely benign (score 0.0634) — an in-silico prediction, not a clinical call.

BMPER p.Pro124Leu

c.371C>T · rs371676663 · VCV1911443

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0634	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -7.24	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 2.3	GERP 0.53, phastCons 0.026
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	20.7	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 0.00769% South Asian · 7/91,066 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00155% 25/1,613,672 alleles · very rare exomes 17/1,461,540 · genomes 8/152,132 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,009
Admixed American	0.00333%	29,991
Remaining individualsnot grpmax-eligible	0.0016%	62,470
Finnishnot grpmax-eligible	0.00156%	64,010
African / African-American	0.00134%	74,898
European (non-Finnish)	0.0011%	90,751

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.Pro124Leu
Coding: c.371C>T
MANE Select: NM_001365308
dbSNP: rs371676663
Type: single nucleotide variant
Location: chr7:33966530 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 124: the vwfc 2 domain

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

Similar variants

BMPER p.Pro124= Conflicting classifications of pathogenicity ★ same residue
BMPER p.Pro124Ser Uncertain significance ★ ⚠ same residue
BMPER p.Arg241Ter Likely pathogenic ★★ same type
BMPER p.Gln309Ter Pathogenic ★★ same type
BMPER p.Ala39Ser Uncertain significance ★★ ⚠ same type
BMPER p.Ala486Val Uncertain significance ★★ ⚠ same type
BMPER p.Arg131Cys Uncertain significance ★★ ⚠ same type
BMPER p.Arg16Ser Uncertain significance ★★ ⚠ same type

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-pro124leu (accessed [today's date]).

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