Is BLM p.Asp1064Asn (c.3190G>A) pathogenic?

BLM p.Asp1064Asn (c.3190G>A) is classified Uncertain significance in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-28). AlphaMissense: ambiguous (0.4369); Absent from gnomAD v4.1; Associated with Bloom syndrome.

What condition is associated with BLM p.Asp1064Asn (c.3190G>A)?

BLM p.Asp1064Asn (c.3190G>A) is associated with Bloom syndrome (ClinVar).

How common is BLM p.Asp1064Asn (c.3190G>A) in the general population?

BLM p.Asp1064Asn (c.3190G>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.Asp1064Asn (c.3190G>A)?

AlphaMissense predicts ambiguous (score 0.4369) — an in-silico prediction, not a clinical call.

BLM p.Asp1064Asn

c.3190G>A · rs1896979510 · VCV1393406

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4369 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Bloom syndrome

Computational evidence

Protein change
AlphaMissense	0.4369	ambiguous
REVEL	0.789	moderately pathogenic-leaning
SaProt	LLR -10.54	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.20	donor gain · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BLM
Protein: p.Asp1064Asn
Coding: c.3190G>A
MANE Select: NM_000057
dbSNP: rs1896979510
Type: single nucleotide variant
Location: chr15:90794337 (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 1064: an α-helix

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.Asp1064Val Likely pathogenic ★★ same residue
BLM p.Asp1064Gly Uncertain significance ★★ ⚠ same residue
BLM p.Asp1064= Likely benign ★ 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-asp1064asn (accessed [today's date]).

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