Is BLM p.Tyr430Ter (c.1289_1290insAT) pathogenic?

BLM p.Tyr430Ter (c.12891290insAT) is classified Pathogenic in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-02). Absent from gnomAD; Associated with Bloom syndrome.

What condition is associated with BLM p.Tyr430Ter (c.1289_1290insAT)?

BLM p.Tyr430Ter (c.1289_1290insAT) is associated with Bloom syndrome (ClinVar).

How common is BLM p.Tyr430Ter (c.1289_1290insAT) in the general population?

BLM p.Tyr430Ter (c.1289_1290insAT) 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.Tyr430Ter

c.1289_1290insAT · rs749512704 · VCV1452830

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

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.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.16	GERP -5.3

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Tyr430Ter
Coding: c.1289_1290insAT
MANE Select: NM_000057
dbSNP: rs749512704
Type: Insertion
Location: chr15:90760662 (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 430: 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.Tyr430Phe Uncertain significance ★★ ⚠ same residue
BLM p.Tyr430= Likely benign ★★ same residue
BLM p.Tyr430_Arg431delinsTer Pathogenic ★ same residue
BLM p.Tyr430His Conflicting classifications of pathogenicity ★ ⚠ same residue
BLM p.Leu751fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Thr1074fs Pathogenic ★★ same condition
BLM p.Ser43_Asp44insTyr Uncertain significance ★★ same condition
BLM p.Thr528delinsIleAla Uncertain significance ★★ 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-tyr430ter (accessed [today's date]).

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