Is BLM p.Val4Asp (c.11T>A) pathogenic?

BLM p.Val4Asp (c.11T>A) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-30). AlphaMissense: likely pathogenic (0.7852); Very rare (popmax 0.00553%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Val4Asp (c.11T>A)?

BLM p.Val4Asp (c.11T>A) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Val4Asp (c.11T>A) in the general population?

BLM p.Val4Asp (c.11T>A) is very rare (popmax 0.00553%, sas) (gnomAD).

What do computational predictors say about BLM p.Val4Asp (c.11T>A)?

AlphaMissense predicts likely pathogenic (score 0.7852) — an in-silico prediction, not a clinical call.

BLM p.Val4Asp

c.11T>A · rs144706057 · VCV1462030

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7852 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00553%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.7852	likely pathogenic
REVEL	0.273	benign-leaning
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	25.4	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 0.00553% South Asian · 5/90,440 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.000412% 6/1,456,944 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00553%	18,088
European (non-Finnish)	8.5e-05%	1,177,012

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.Val4Asp
Coding: c.11T>A
MANE Select: NM_000057
dbSNP: rs144706057
Type: single nucleotide variant
Location: chr15:90747403 (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 4: the 'disordered' region

Full BLM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bloom syndrome

Similar variants

BLM p.Val4Phe Uncertain significance ★★ ⚠ same residue
BLM p.Val4Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BLM p.Val4Ile Uncertain significance ★ ⚠ same residue
BLM p.Val4Leu Uncertain significance ★ ⚠ same residue
BLM p.Val4= Uncertain significance same residue
BLM p.Val4fs Likely pathogenic ★ same residue
BLM c.1087+1G>A Likely pathogenic ★★ same condition
BLM c.1088-1G>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-val4asp (accessed [today's date]).

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