Is BLM p.Ala790Glu (c.2369C>A) pathogenic?

BLM p.Ala790Glu (c.2369C>A) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-26). AlphaMissense: likely pathogenic (0.5989); Absent from gnomAD v4.1; Associated with Bloom syndrome.

What condition is associated with BLM p.Ala790Glu (c.2369C>A)?

BLM p.Ala790Glu (c.2369C>A) is associated with Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Ala790Glu (c.2369C>A) in the general population?

BLM p.Ala790Glu (c.2369C>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.Ala790Glu (c.2369C>A)?

AlphaMissense predicts likely pathogenic (score 0.5989) — an in-silico prediction, not a clinical call.

BLM p.Ala790Glu

c.2369C>A · rs2151165767 · VCV2452577

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5989 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bloom syndrome

Computational evidence

Protein change
AlphaMissense	0.5989	likely pathogenic
REVEL	0.473	indeterminate
SaProt	LLR -10.51	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Ala790Glu
Coding: c.2369C>A
MANE Select: NM_000057
dbSNP: rs2151165767
Type: single nucleotide variant
Location: chr15:90769194 (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 790: the helicase atp-binding domain; a β-strand

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.Ala790Pro Uncertain significance ★★ ⚠ same residue
BLM p.Ala790Thr Uncertain significance ★★ ⚠ same residue
BLM p.Ala790Val Uncertain significance ★★ ⚠ same residue
BLM p.Ala790= Likely benign ★★ same residue
BLM p.Ala790Gly Uncertain significance ★ ⚠ same residue
BLM p.Ala790Ser Uncertain significance ★ ⚠ 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-ala790glu (accessed [today's date]).

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