Is BLM p.Ile720= (c.2160C>T) pathogenic?

BLM p.Ile720= (c.2160C>T) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.01%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ile720= (c.2160C>T)?

BLM p.Ile720= (c.2160C>T) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Ile720= (c.2160C>T) in the general population?

BLM p.Ile720= (c.2160C>T) is low-frequency (popmax 1.01%, afr) (gnomAD).

BLM p.Ile720=

c.2160C>T · rs28385028 · VCV136513

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.01%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.93	GERP -5.5, phastCons 0.99
Overall
CADD	6.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.01% African / African-American · 758/74,986 alleles

Filtering AF 0.951% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.927%

Overall 0.0533% 859/1,612,632 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.01%	99
Admixed American	0.065%	1,539
Remaining individualsnot grpmax-eligible	0.056%	1,784
Middle Eastern	0.0495%	2,019
South Asian	0.0033%	30,348
European (non-Finnish)	0.00178%	56,132

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.Ile720=
Coding: c.2160C>T
MANE Select: NM_000057
dbSNP: rs28385028
Type: single nucleotide variant
Location: chr15:90765381 (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 720: the helicase atp-binding domain; an α-helix

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.Ile720Thr Uncertain significance ★★ ⚠ same residue
BLM p.Ile720Val 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
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

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-ile720 (accessed [today's date]).

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