Is BMPR1B p.Ala6= (c.18A>G) pathogenic?

BMPR1B p.Ala6= (c.18A>G) is classified Likely benign in BMPR1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-06). Rare (popmax 0.147%, sas); Associated with brachydactyly type A2.

What condition is associated with BMPR1B p.Ala6= (c.18A>G)?

BMPR1B p.Ala6= (c.18A>G) is associated with brachydactyly type A2, acromesomelic dysplasia 3 (ClinVar).

How common is BMPR1B p.Ala6= (c.18A>G) in the general population?

BMPR1B p.Ala6= (c.18A>G) is rare (popmax 0.147%, sas) (gnomAD).

BMPR1B p.Ala6=

c.18A>G · rs536960015 · VCV1126554

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.147%, sas)

Conditions

brachydactyly type A2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -0.087, phastCons 1
Overall
CADD	10.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.147% South Asian · 134/91,062 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.119%

Overall 0.00874% 141/1,613,354 alleles · rare exomes 130/1,461,176 · genomes 11/152,178 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.147%	680
Middle Eastern	0.033%	3,029
Remaining individualsnot grpmax-eligible	0.0064%	15,620
European (non-Finnish)	8.48e-05%	1,179,558

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: BMPR1B
Protein: p.Ala6=
Coding: c.18A>G
MANE Select: NM_001203
dbSNP: rs536960015
Type: single nucleotide variant
Location: chr4:95104442 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.36 · 1 PDB
Residue 6: the 'disordered' region

Full BMPR1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

brachydactyly type A2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acromesomelic dysplasia 3

Similar variants

BMPR1B p.Ala6Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BMPR1B c.585+1G>C Likely pathogenic ★★ same condition
BMPR1B p.Arg486Trp Pathogenic ★★ same condition
BMPR1B p.Arg412Gly Uncertain significance ★★ ⚠ same condition
BMPR1B p.Arg91Ile Uncertain significance ★★ ⚠ same condition
BMPR1B p.Asn257Asp Uncertain significance ★★ ⚠ same condition
BMPR1B p.Asp166Gly Uncertain significance ★★ ⚠ same condition
BMPR1B p.Asp280Asn 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/bmpr1b-p-ala6 (accessed [today's date]).

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