Is BLMH p.Arg72Gln (c.215G>A) pathogenic?

BLMH p.Arg72Gln (c.215G>A) is classified Uncertain significance in BLMH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: likely pathogenic (0.9329); Very rare (popmax 0.00224%, eas).

How common is BLMH p.Arg72Gln (c.215G>A) in the general population?

BLMH p.Arg72Gln (c.215G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about BLMH p.Arg72Gln (c.215G>A)?

AlphaMissense predicts likely pathogenic (score 0.9329) — an in-silico prediction, not a clinical call.

BLMH p.Arg72Gln

c.215G>A · rs755776639 · VCV2550399

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9329	likely pathogenic
REVEL	0.591	indeterminate
SaProt	LLR -13.29	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 1,884 bp · p 0.001 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00224% East Asian · 1/44,692 alleles

Filtering AF 0.00146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00174% 28/1,605,866 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,692
European (non-Finnish)	0.00213%	47,019
Admixed American	0.00169%	59,068
Remaining individualsnot grpmax-eligible	0.00161%	62,086

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: BLMH
Protein: p.Arg72Gln
Coding: c.215G>A
MANE Select: NM_000386
dbSNP: rs755776639
Type: single nucleotide variant
Location: chr17:30289479 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 98.10 · 6 PDB

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

Similar variants

BLMH p.Ala117Gly Uncertain significance ★ ⚠ same type
BLMH p.Ala13Val Uncertain significance ★ ⚠ same type
BLMH p.Ala313Val Uncertain significance ★ ⚠ same type
BLMH p.Ala314Ser Uncertain significance ★ ⚠ same type
BLMH p.Ala314Val Uncertain significance ★ ⚠ same type
BLMH p.Arg191Leu Uncertain significance ★ ⚠ same type
BLMH p.Arg43Trp Uncertain significance ★ same type
BLMH p.Asn241Ile 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/blmh-p-arg72gln (accessed [today's date]).

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