Is BMP6 p.Ser192Phe (c.575C>T) pathogenic?

BMP6 p.Ser192Phe (c.575C>T) is classified Uncertain significance in BMP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: likely benign (0.0913); Absent from gnomAD v4.1.

How common is BMP6 p.Ser192Phe (c.575C>T) in the general population?

BMP6 p.Ser192Phe (c.575C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMP6 p.Ser192Phe (c.575C>T)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

BMP6 p.Ser192Phe

c.575C>T · VCV3824674

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -9.60	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 1.6	GERP -0.2, phastCons 0.55
Regional constraint	o/e 1.17	unconstrained · MANE · 152 kb · p 7.1e-05 · regional, not allelic
Overall
CADD	17.18	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

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: BMP6
Protein: p.Ser192Phe
Coding: c.575C>T
MANE Select: NM_001718
Type: single nucleotide variant
Location: chr6:7727530 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 69.74 · 5 PDB
Residue 192: a UniProt-annotated variant site (in io; associated with disease susceptibility); the 'disordered' region

Full BMP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP6 p.Leu209Pro Uncertain significance ★★ ⚠ same type
BMP6 p.Ser160= Benign/Likely benign ★★ same type
BMP6 p.Leu137Met Likely pathogenic ★ ⚠ same type
BMP6 c.-377G>A Uncertain significance ★ same type
BMP6 p.Ala142Thr Uncertain significance ★ ⚠ same type
BMP6 p.Ala152Glu Uncertain significance ★ ⚠ same type
BMP6 p.Ala203Ser Uncertain significance ★ ⚠ same type
BMP6 p.Ala254Thr 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/bmp6-p-ser192phe (accessed [today's date]).

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