Is BLM p.Lys137Arg (c.410A>G) pathogenic?

BLM p.Lys137Arg (c.410A>G) is classified Benign/Likely benign in BLM (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-06-22). AlphaMissense: likely benign (0.0826); Low-frequency (popmax 1.35%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Lys137Arg (c.410A>G)?

BLM p.Lys137Arg (c.410A>G) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Lys137Arg (c.410A>G) in the general population?

BLM p.Lys137Arg (c.410A>G) is low-frequency (popmax 1.35%, afr) (gnomAD).

What do computational predictors say about BLM p.Lys137Arg (c.410A>G)?

AlphaMissense predicts likely benign (score 0.0826) — an in-silico prediction, not a clinical call.

BLM p.Lys137Arg

c.410A>G · rs28384988 · VCV133707

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

AlphaMissense

likely benign

0.0826 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.35%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0826	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -6.62	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 7.1	GERP 1.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	22.0	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 1.35% African / African-American · 1,013/75,058 alleles

Filtering AF 1.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.25%

Overall 0.0763% 1,232/1,614,194 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.35%	74
Middle Eastern	0.148%	674
Admixed American	0.11%	909
Remaining individualsnot grpmax-eligible	0.107%	933
European (non-Finnish)	0.00627%	15,946
East Asian	0.00223%	44,876
South Asian	0.0022%	45,545

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.Lys137Arg
Coding: c.410A>G
MANE Select: NM_000057
dbSNP: rs28384988
Type: single nucleotide variant
Location: chr15:90749678 (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 137: a UniProt-annotated variant site (in)

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 p.Lys137Glu Uncertain significance ★★ ⚠ same residue
BLM p.Lys137= Likely benign ★★ same residue
BLM p.Lys137Asn Uncertain significance ★ ⚠ same residue
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

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-lys137arg (accessed [today's date]).

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