Is BLM p.Glu413Lys (c.1237G>A) pathogenic?

BLM p.Glu413Lys (c.1237G>A) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-03-10). AlphaMissense: likely benign (0.0883); Ultra-rare (popmax 0.012%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Glu413Lys (c.1237G>A)?

BLM p.Glu413Lys (c.1237G>A) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Glu413Lys (c.1237G>A) in the general population?

BLM p.Glu413Lys (c.1237G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about BLM p.Glu413Lys (c.1237G>A)?

AlphaMissense predicts likely benign (score 0.0883) — an in-silico prediction, not a clinical call.

BLM p.Glu413Lys

c.1237G>A · rs887921909 · VCV454072

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0883 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0883	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -5.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.57 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	14.77	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 0.012% African / African-American · 9/74,856 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00199% 32/1,611,320 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,317
European (non-Finnish)	0.00178%	56,117
Admixed American	0.00167%	59,892
Remaining individualsnot grpmax-eligible	0.0016%	62,364

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.Glu413Lys
Coding: c.1237G>A
MANE Select: NM_000057
dbSNP: rs887921909
Type: single nucleotide variant
Location: chr15:90760610 (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 413: the 'necessary for interaction with spidr' region; the 'necessary for dimerization and homooligomerization' 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 p.Glu413Ter Pathogenic/Likely pathogenic ★★ same residue
BLM p.Glu413Val Uncertain significance ★★ ⚠ same residue
BLM p.Glu413Gln Uncertain significance ★ ⚠ same residue
BLM p.Glu413Gly Uncertain significance ★ ⚠ same residue
BLM p.Glu413fs Pathogenic ★ 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

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-glu413lys (accessed [today's date]).

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