Is BLM p.Arg489= (c.1467G>A) pathogenic?

BLM p.Arg489= (c.1467G>A) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-02-02). Rare (popmax 0.123%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Arg489= (c.1467G>A)?

BLM p.Arg489= (c.1467G>A) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Arg489= (c.1467G>A) in the general population?

BLM p.Arg489= (c.1467G>A) is rare (popmax 0.123%, afr) (gnomAD).

BLM p.Arg489=

c.1467G>A · rs56257041 · VCV236801

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.123%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP -5.3, phastCons 0.15
Overall
CADD	0.667	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.123% African / African-American · 92/75,000 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0948%

Overall 0.0149% 241/1,613,974 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.123%	815
Middle Eastern	0.099%	1,010
Remaining individualsnot grpmax-eligible	0.0384%	2,604
Admixed American	0.0183%	5,456
European (non-Finnish)	0.00907%	11,028
South Asian	0.0011%	91,074

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: BLM
Protein: p.Arg489=
Coding: c.1467G>A
MANE Select: NM_000057
dbSNP: rs56257041
Type: single nucleotide variant
Location: chr15:90760840 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 61.10 · 16 PDB
Residue 489: the 'necessary for interaction with spidr' region

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bloom syndrome

Similar variants

BLM c.1087+1G>A Likely pathogenic ★★ same condition
BLM c.1088-1G>A Likely pathogenic ★★ same condition
BLM c.1220+2T>C Likely pathogenic ★★ same condition
BLM c.1220+2T>G Likely pathogenic ★★ same condition
BLM c.1882+2T>C Likely pathogenic ★★ same condition
BLM c.2074+1G>T Likely pathogenic ★★ same condition
BLM c.2075-1G>A Likely pathogenic ★★ same condition
BLM c.2193+1G>A Pathogenic/Likely pathogenic ★★ same condition

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/blm-p-arg489 (accessed [today's date]).

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