Is BMF p.Arg135Gln (c.404G>A) pathogenic?

BMF p.Arg135Gln (c.404G>A) is classified Uncertain significance in BMF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). AlphaMissense: likely benign (0.0939); Very rare (popmax 0.00333%, amr).

How common is BMF p.Arg135Gln (c.404G>A) in the general population?

BMF p.Arg135Gln (c.404G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about BMF p.Arg135Gln (c.404G>A)?

AlphaMissense predicts likely benign (score 0.0939) — an in-silico prediction, not a clinical call.

BMF p.Arg135Gln

c.404G>A · VCV3481100

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0939 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0939	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -5.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.17 · regional, not allelic
Overall
CADD	22.5	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 0.00333% Admixed American · 2/60,010 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000681% 11/1,614,092 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,005
European (non-Finnish)	0.000763%	131,116

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.Arg135Gln
Coding: c.404G>A
MANE Select: NM_001003940
Type: single nucleotide variant
Location: chr15:40104229 (GRCh38)
Gene constraint: LOEUF 0.788 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 62.81 · 5 PDB
Residue 135: an α-helix

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.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
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-arg135gln (accessed [today's date]).

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