Is BLM p.Ala1136Phe (c.3406_3407delinsTT) pathogenic?

BLM p.Ala1136Phe (c.34063407delinsTT) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-10). Absent from gnomAD; Associated with Bloom syndrome.

What condition is associated with BLM p.Ala1136Phe (c.3406_3407delinsTT)?

BLM p.Ala1136Phe (c.3406_3407delinsTT) is associated with Bloom syndrome (ClinVar).

How common is BLM p.Ala1136Phe (c.3406_3407delinsTT) in the general population?

BLM p.Ala1136Phe (c.3406_3407delinsTT) is absent from gnomAD (gnomAD).

How is Bloom syndrome inherited?

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

BLM p.Ala1136Phe

c.3406_3407delinsTT · rs2151194224 · VCV1393180

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Bloom syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.4	GERP -4.8
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ala1136Phe
Coding: c.3406_3407delinsTT
MANE Select: NM_000057
dbSNP: rs2151194224
Type: Indel
Location: chr15:90803568 (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 1136: the 'dna holliday junction binding' region; a turn

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.Ala1136Pro Uncertain significance ★★ ⚠ same residue
BLM p.Ala1136Val Conflicting classifications of pathogenicity ★ ⚠ same residue
BLM p.Asn1141fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Met1190fs Pathogenic/Likely pathogenic ★★ same condition
BLM c.799+4_799+5delinsCA Uncertain significance ★★ same condition
BLM p.Phe561Asp Uncertain significance ★★ same condition
BLM p.Thr994Lys Uncertain significance ★★ same condition
BLM p.Glu1035Ter 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-ala1136phe (accessed [today's date]).

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