Is BMP8A p.Asn346Ser (c.1037A>G) pathogenic?

BMP8A p.Asn346Ser (c.1037A>G) is classified Uncertain significance in BMP8A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-23). AlphaMissense: likely benign (0.314); Very rare (popmax 0.00401%, afr).

How common is BMP8A p.Asn346Ser (c.1037A>G) in the general population?

BMP8A p.Asn346Ser (c.1037A>G) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about BMP8A p.Asn346Ser (c.1037A>G)?

AlphaMissense predicts likely benign (score 0.314) — an in-silico prediction, not a clinical call.

BMP8A p.Asn346Ser

c.1037A>G · VCV3824689

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.314 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.314	likely benign
REVEL	0.679	pathogenic-leaning
SaProt	LLR -10.91	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 3,377 bp · p 0.12 · regional, not allelic
Overall
CADD	23.9	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 0.00401% African / African-American · 3/74,792 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000806% 13/1,613,612 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,931
European (non-Finnish)	0.000848%	117,991

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: BMP8A
Protein: p.Asn346Ser
Coding: c.1037A>G
MANE Select: NM_181809
Type: single nucleotide variant
Location: chr1:39523095 (GRCh38)
Gene constraint: LOEUF 1.337 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.87
Residue 346: a disulfide bond

Full BMP8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP8A p.Ala144Val Uncertain significance ★★ ⚠ same type
BMP8A p.Arg293His Benign ★★ same type
BMP8A p.Ala102Thr Uncertain significance ★ ⚠ same type
BMP8A p.Ala201Thr Uncertain significance ★ ⚠ same type
BMP8A p.Ala264Thr Uncertain significance ★ ⚠ same type
BMP8A p.Ala348Val Uncertain significance ★ ⚠ same type
BMP8A p.Ala365Val Uncertain significance ★ ⚠ same type
BMP8A p.Ala374Thr 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/bmp8a-p-asn346ser (accessed [today's date]).

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