Is BMS1 p.Ser295fs (c.883del) pathogenic?

BMS1 p.Ser295fs (c.883del) is classified Uncertain significance in BMS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). Ultra-rare (popmax 0.0215%, afr); Associated with aplasia cutis congenita.

What condition is associated with BMS1 p.Ser295fs (c.883del)?

BMS1 p.Ser295fs (c.883del) is associated with aplasia cutis congenita (ClinVar).

How common is BMS1 p.Ser295fs (c.883del) in the general population?

BMS1 p.Ser295fs (c.883del) is ultra-rare (popmax 0.0215%, afr) (gnomAD).

BMS1 p.Ser295fs

c.883del · VCV3893003

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0215%, afr)

Conditions

aplasia cutis congenita

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.3	GERP 0.74, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0215% African / African-American · 16/74,562 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.0178% 27/151,630 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0215%	4,660
East Asian	0.0067%	14,915
Admixed American	0.00501%	19,955
South Asian	0.0033%	30,291
European (non-Finnish)	0.00017%	589,751

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: BMS1
Protein: p.Ser295fs
Coding: c.883del
MANE Select: NM_014753
Type: Deletion
Location: chr10:42792593 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 72.04 · 3 PDB

Full BMS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

aplasia cutis congenita — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMS1 p.Leu732Val Uncertain significance ★ ⚠ same condition
BMS1 p.Pro742Leu Uncertain significance ★ ⚠ same condition
BMS1 p.Arg930His Pathogenic same condition
BMS1 c.3457-14_3457-11del Likely benign 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/bms1-p-ser295fs (accessed [today's date]).

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