Is BLM p.Leu511Gln (c.1532T>A) pathogenic?

BLM p.Leu511Gln (c.1532T>A) is classified Uncertain significance in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-19). AlphaMissense: likely benign (0.0684); Absent from gnomAD v4.1; Associated with Bloom syndrome.

What condition is associated with BLM p.Leu511Gln (c.1532T>A)?

BLM p.Leu511Gln (c.1532T>A) is associated with Bloom syndrome (ClinVar).

How common is BLM p.Leu511Gln (c.1532T>A) in the general population?

BLM p.Leu511Gln (c.1532T>A) is absent from gnomAD v4.1 (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.Leu511Gln (c.1532T>A)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

BLM p.Leu511Gln

c.1532T>A · rs1446287900 · VCV1061658

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,972)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bloom syndrome

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -7.04	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 -2.9	GERP -5.3
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	2.556	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

No allele count reported in gnomAD v4.1 (AN 1,612,972). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BLM
Protein: p.Leu511Gln
Coding: c.1532T>A
MANE Select: NM_000057
dbSNP: rs1446287900
Type: single nucleotide variant
Location: chr15:90760905 (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 511: the 'necessary for interaction with spidr' region

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.Leu511Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
BLM p.Leu511= Likely benign ★ same residue
BLM p.Leu511Val 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-leu511gln (accessed [today's date]).

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