Is BLM p.Asp1010Val (c.3029A>T) pathogenic?

BLM p.Asp1010Val (c.3029A>T) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-10). AlphaMissense: ambiguous (0.4175); Ultra-rare (popmax 0.018%, eas); Associated with Bloom syndrome.

What condition is associated with BLM p.Asp1010Val (c.3029A>T)?

BLM p.Asp1010Val (c.3029A>T) is associated with Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Asp1010Val (c.3029A>T) in the general population?

BLM p.Asp1010Val (c.3029A>T) is ultra-rare (popmax 0.018%, eas) (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.Asp1010Val (c.3029A>T)?

AlphaMissense predicts ambiguous (score 0.4175) — an in-silico prediction, not a clinical call.

BLM p.Asp1010Val

c.3029A>T · rs1459742200 · VCV576518

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4175 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.018%, eas)

Conditions

Bloom syndrome

Computational evidence

Protein change
AlphaMissense	0.4175	ambiguous
REVEL	0.56	indeterminate
SaProt	LLR -10.33	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	24.1	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

Grpmax group 0.018% East Asian · 8/44,362 alleles

Filtering AF 0.00892% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00647%

Overall 0.0005% 8/1,600,894 alleles · ultra-rare exomes 8/1,448,606 · genomes 0/152,288 · joint denominator

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.Asp1010Val
Coding: c.3029A>T
MANE Select: NM_000057
dbSNP: rs1459742200
Type: single nucleotide variant
Location: chr15:90794176 (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 1010: the helicase c-terminal domain

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

Also linked: hereditary neoplastic syndrome

For Bloom syndrome (Orphanet):

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

Similar variants

BLM p.Asp1010fs Pathogenic/Likely pathogenic ★★ 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
BLM c.2074+1G>T Likely pathogenic ★★ same condition
BLM c.2075-1G>A 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-asp1010val (accessed [today's date]).

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