Is BMF p.Asp12Asn (c.34G>A) pathogenic?

BMF p.Asp12Asn (c.34G>A) is classified Uncertain significance in BMF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely pathogenic (0.6054); Very rare (popmax 0.00167%, amr).

How common is BMF p.Asp12Asn (c.34G>A) in the general population?

BMF p.Asp12Asn (c.34G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BMF p.Asp12Asn (c.34G>A)?

AlphaMissense predicts likely pathogenic (score 0.6054) — an in-silico prediction, not a clinical call.

BMF p.Asp12Asn

c.34G>A · VCV4214222

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6054 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6054	likely pathogenic
REVEL	0.224	benign-leaning
SaProt	LLR -7.39	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.17 · regional, not allelic
Overall
CADD	27.6	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 0.00167% Admixed American · 1/59,872 alleles

Overall 6.85e-05% 1/1,458,916 alleles · very rare

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: BMF
Protein: p.Asp12Asn
Coding: c.34G>A
MANE Select: NM_001003940
Type: single nucleotide variant
Location: chr15:40106053 (GRCh38)
Gene constraint: LOEUF 0.788 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 62.81 · 5 PDB

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

Similar variants

BMF p.Ala100Thr Uncertain significance ★ ⚠ same type
BMF p.Ala171Thr Uncertain significance ★ ⚠ same type
BMF p.Arg103Leu Uncertain significance ★ ⚠ same type
BMF p.Arg135Gln Uncertain significance ★ ⚠ same type
BMF p.Arg94Gln Uncertain significance ★ ⚠ same type
BMF p.Gln16His Uncertain significance ★ ⚠ same type
BMF p.Glu118Val Uncertain significance ★ ⚠ same type
BMF p.Glu176Gln 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/bmf-p-asp12asn (accessed [today's date]).

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