Is BMF p.Glu2Gln (c.4G>C) pathogenic?

BMF p.Glu2Gln (c.4G>C) is classified Uncertain significance in BMF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.1192); Rare (popmax 0.234%, mid).

How common is BMF p.Glu2Gln (c.4G>C) in the general population?

BMF p.Glu2Gln (c.4G>C) is rare (popmax 0.234%, mid) (gnomAD).

What do computational predictors say about BMF p.Glu2Gln (c.4G>C)?

AlphaMissense predicts likely benign (score 0.1192) — an in-silico prediction, not a clinical call.

BMF p.Glu2Gln

c.4G>C · rs370152086 · VCV2282220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1192 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.234%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1192	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -7.43	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 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.17 · regional, not allelic
Overall
CADD	26.7	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

Grpmax group 0.234% Middle Eastern · 14/5,992 alleles

Filtering AF 0.141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.113%

Overall 0.0193% 309/1,598,040 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.234%	428
South Asian	0.0639%	1,566
Remaining individualsnot grpmax-eligible	0.0469%	2,134
Admixed American	0.0439%	2,277
European (non-Finnish)	0.015%	6,655
African / African-American	0.00668%	14,971
East Asian	0.00448%	22,324

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.Glu2Gln
Coding: c.4G>C
MANE Select: NM_001003940
dbSNP: rs370152086
Type: single nucleotide variant
Location: chr15:40106083 (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.Asp12Asn Uncertain significance ★ ⚠ same type
BMF p.Gln16His Uncertain significance ★ ⚠ same type
BMF p.Glu118Val 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-glu2gln (accessed [today's date]).

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