Is BMPER p.Val660Ile (c.1978G>A) pathogenic?

BMPER p.Val660Ile (c.1978G>A) is classified Conflicting classifications of pathogenicity in BMPER (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-03). AlphaMissense: likely benign (0.069); Ultra-rare (popmax 0.015%, amr); Associated with Inborn genetic diseases.

What condition is associated with BMPER p.Val660Ile (c.1978G>A)?

BMPER p.Val660Ile (c.1978G>A) is associated with Inborn genetic diseases, diaphanospondylodysostosis (ClinVar).

How common is BMPER p.Val660Ile (c.1978G>A) in the general population?

BMPER p.Val660Ile (c.1978G>A) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about BMPER p.Val660Ile (c.1978G>A)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

BMPER p.Val660Ile

c.1978G>A · rs376351419 · VCV360119

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -7.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.8	GERP -5.5
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	0.135	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 0.015% Admixed American · 9/59,986 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00545% 88/1,613,948 alleles · ultra-rare exomes 77/1,461,820 · genomes 11/152,128 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,665
Remaining individualsnot grpmax-eligible	0.0064%	15,620
European (non-Finnish)	0.00602%	16,619
African / African-American	0.00401%	24,968
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Val660Ile
Coding: c.1978G>A
MANE Select: NM_001365308
dbSNP: rs376351419
Type: single nucleotide variant
Location: chr7:34153193 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 660: the til 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

Also linked: diaphanospondylodysostosis

Similar variants

BMPER p.Val660Ala Uncertain significance ★ ⚠ same residue
BMPER p.Arg241Ter Likely pathogenic ★★ same condition
BMPER p.Gln309Ter Pathogenic ★★ same condition
BMPER p.Ala39Ser Uncertain significance ★★ ⚠ same condition
BMPER p.Ala486Val Uncertain significance ★★ ⚠ same condition
BMPER p.Arg131Cys Uncertain significance ★★ ⚠ same condition
BMPER p.Arg16Ser Uncertain significance ★★ ⚠ same condition
BMPER p.Arg332His 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-val660ile (accessed [today's date]).

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