Is BLM p.Lys347Glu (c.1039A>G) pathogenic?

BLM p.Lys347Glu (c.1039A>G) is classified Uncertain significance in BLM (ClinVar, Single submitter, 2 submitters; last evaluated 2024-10-22). AlphaMissense: likely benign (0.0678); Very rare (popmax 0.00267%, afr); Associated with Bloom syndrome.

What condition is associated with BLM p.Lys347Glu (c.1039A>G)?

BLM p.Lys347Glu (c.1039A>G) is associated with Bloom syndrome (ClinVar).

How common is BLM p.Lys347Glu (c.1039A>G) in the general population?

BLM p.Lys347Glu (c.1039A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Bloom syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BLM p.Lys347Glu (c.1039A>G)?

AlphaMissense predicts likely benign (score 0.0678) — an in-silico prediction, not a clinical call.

BLM p.Lys347Glu

c.1039A>G · rs375250788 · VCV861487

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0678 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bloom syndrome

Computational evidence

Protein change
AlphaMissense	0.0678	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -5.84	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 1	GERP -4.9, phastCons 0.97
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	12.5	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 0.00267% African / African-American · 2/74,908 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,864 alleles · very rare exomes 1/1,461,694 · genomes 2/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,454
European (non-Finnish)	8.47e-05%	1,179,965

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.Lys347Glu
Coding: c.1039A>G
MANE Select: NM_000057
dbSNP: rs375250788
Type: single nucleotide variant
Location: chr15:90754890 (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 347: the 'necessary for interaction with spidr' region; a cross-link site

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

Disease context

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

For Bloom syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BLM p.Lys347= Likely benign ★ same residue
BLM p.Lys347fs Likely pathogenic ★ same residue
BLM p.Lys347Thr 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-lys347glu (accessed [today's date]).

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