Is BMP1 p.Ser353Phe (c.1058C>T) pathogenic?

BMP1 p.Ser353Phe (c.1058C>T) is classified Uncertain significance in BMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-24). AlphaMissense: likely pathogenic (0.7687); Absent from gnomAD v4.1.

How common is BMP1 p.Ser353Phe (c.1058C>T) in the general population?

BMP1 p.Ser353Phe (c.1058C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMP1 p.Ser353Phe (c.1058C>T)?

AlphaMissense predicts likely pathogenic (score 0.7687) — an in-silico prediction, not a clinical call.

BMP1 p.Ser353Phe

c.1058C>T · rs2538985693 · VCV2114610

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7687 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7687	likely pathogenic
REVEL	0.454	indeterminate
SaProt	LLR -12.48	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 35 kb · p 1e-07 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMP1
Protein: p.Ser353Phe
Coding: c.1058C>T
MANE Select: NM_006129
dbSNP: rs2538985693
Type: single nucleotide variant
Location: chr8:22180464 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB
Residue 353: the cub 1 domain

Full BMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP1 p.Ser353= Likely benign ★ same residue
BMP1 p.Cys183Ter Pathogenic/Likely pathogenic ★★ same type
BMP1 p.Gln70Ter Pathogenic/Likely pathogenic ★★ same type
BMP1 c.1443+6T>C Uncertain significance ★★ same type
BMP1 c.1639+4C>G Uncertain significance ★★ same type
BMP1 c.2233+4C>T Uncertain significance ★★ same type
BMP1 c.*452A>C Uncertain significance ★★ same type
BMP1 p.Ala538Val 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/bmp1-p-ser353phe (accessed [today's date]).

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