Is BMP6 p.Ser144Phe (c.431C>T) pathogenic?

BMP6 p.Ser144Phe (c.431C>T) is classified Uncertain significance in BMP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: ambiguous (0.3879); Very rare (popmax 0.00221%, sas).

How common is BMP6 p.Ser144Phe (c.431C>T) in the general population?

BMP6 p.Ser144Phe (c.431C>T) is very rare (popmax 0.00221%, sas) (gnomAD).

What do computational predictors say about BMP6 p.Ser144Phe (c.431C>T)?

AlphaMissense predicts ambiguous (score 0.3879) — an in-silico prediction, not a clinical call.

BMP6 p.Ser144Phe

c.431C>T · VCV4646228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

Computational evidence

Protein change
AlphaMissense	0.3879	ambiguous
REVEL	0.38	indeterminate
SaProt	LLR -10.07	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 1.5, phastCons 0.98
Regional constraint	o/e 1.17	unconstrained · MANE · 152 kb · p 7.1e-05 · regional, not allelic
Overall
CADD	25.6	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 0.00221% South Asian · 2/90,532 alleles

Filtering AF 0.000765% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000606%

Overall 0.00106% 17/1,608,260 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00221%	45,266
European (non-Finnish)	0.00127%	78,534

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: BMP6
Protein: p.Ser144Phe
Coding: c.431C>T
MANE Select: NM_001718
Type: single nucleotide variant
Location: chr6:7727386 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 69.74 · 5 PDB

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

Similar variants

BMP6 p.Ser144Thr Uncertain significance ★ ⚠ same residue
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

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-ser144phe (accessed [today's date]).

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