Is BLM p.Phe807Cys (c.2420T>G) pathogenic?

BLM p.Phe807Cys (c.2420T>G) is classified Uncertain significance in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-06). AlphaMissense: likely pathogenic (0.9981); Very rare (popmax 8.47e-05%, nfe); Associated with Bloom syndrome.

What condition is associated with BLM p.Phe807Cys (c.2420T>G)?

BLM p.Phe807Cys (c.2420T>G) is associated with Bloom syndrome (ClinVar).

How common is BLM p.Phe807Cys (c.2420T>G) in the general population?

BLM p.Phe807Cys (c.2420T>G) is very rare (popmax 8.47e-05%, nfe) (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.Phe807Cys (c.2420T>G)?

AlphaMissense predicts likely pathogenic (score 0.9981) — an in-silico prediction, not a clinical call.

BLM p.Phe807Cys

c.2420T>G · rs2505456384 · VCV2847722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9981 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bloom syndrome

Computational evidence

Protein change
AlphaMissense	0.9981	likely pathogenic · top 1% in BLM
REVEL	0.93	moderately pathogenic-leaning
SaProt	LLR -14.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	31.0	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,022 alleles

Overall 6.2e-05% 1/1,614,152 alleles · very rare exomes 1/1,461,886 · genomes 0/152,266 · 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.Phe807Cys
Coding: c.2420T>G
MANE Select: NM_000057
dbSNP: rs2505456384
Type: single nucleotide variant
Location: chr15:90769451 (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 807: the helicase atp-binding domain; a turn

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.Phe807Ile Uncertain significance ★★ ⚠ same residue
BLM p.Phe807= Likely benign ★★ same residue
BLM p.Phe807Leu Uncertain significance ★ ⚠ same residue
BLM p.Phe807fs Pathogenic ★ same residue
BLM p.Phe807Ser Uncertain significance ★ ⚠ 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

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-phe807cys (accessed [today's date]).

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