Is BMPER p.Tyr253= (c.759C>T) pathogenic?

BMPER p.Tyr253= (c.759C>T) is classified Likely benign in BMPER (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-27). Ultra-rare (popmax 0.0133%, afr).

How common is BMPER p.Tyr253= (c.759C>T) in the general population?

BMPER p.Tyr253= (c.759C>T) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

BMPER p.Tyr253=

c.759C>T · rs377437543 · VCV1633745

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.46 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.8	GERP -4.3
Overall
CADD	1.236	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% African / African-American · 10/75,002 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00384% 62/1,613,778 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0144%	6,944
African / African-Americangrpmax	0.0133%	7,500
Admixed American	0.00833%	12,004
Finnishnot grpmax-eligible	0.00625%	16,006
European (non-Finnish)	0.00271%	36,866
South Asian	0.0022%	45,536

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr253=
Coding: c.759C>T
MANE Select: NM_001365308
dbSNP: rs377437543
Type: single nucleotide variant
Location: chr7:34051943 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 253: the vwfc 4 domain

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

Similar variants

BMPER p.Tyr253Cys 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
BMPER p.Arg332His 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-tyr253 (accessed [today's date]).

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