Is BLM p.Ser696fs (c.2086_2087del) pathogenic?

BLM p.Ser696fs (c.20862087del) is classified Pathogenic/Likely pathogenic in BLM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-09). Very rare (popmax 0.000256%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ser696fs (c.2086_2087del)?

BLM p.Ser696fs (c.2086_2087del) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Ser696fs (c.2086_2087del) in the general population?

BLM p.Ser696fs (c.2086_2087del) is very rare (popmax 0.000256%, nfe) (gnomAD).

BLM p.Ser696fs

c.2086_2087del · rs2505441027 · VCV1785639

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000256%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000256% European (non-Finnish) · 3/1,173,956 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000187% 3/1,607,428 alleles · very rare exomes 3/1,455,150 · genomes 0/152,278 · 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.Ser696fs
Coding: c.2086_2087del
MANE Select: NM_000057
dbSNP: rs2505441027
Type: Microsatellite
Location: chr15:90765305 (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 696: the helicase atp-binding domain; an α-helix; a binding site

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.Ser696Asn Uncertain significance ★★ ⚠ same residue
BLM p.Ser696Gly Uncertain significance ★★ ⚠ same residue
BLM p.Ser696= Likely benign ★★ same residue
BLM p.Arg191fs Pathogenic ★★ same condition
BLM p.Asn202fs Pathogenic ★★ same condition
BLM p.Asn782fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Cys361_Asp362delinsTer Pathogenic ★★ same condition
BLM p.Gln100fs Pathogenic/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-ser696fs (accessed [today's date]).

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