Is BLM p.Cys1055= (c.3165T>C) pathogenic?

BLM p.Cys1055= (c.3165T>C) is classified Likely benign in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-15). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Cys1055= (c.3165T>C)?

BLM p.Cys1055= (c.3165T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Cys1055= (c.3165T>C) in the general population?

BLM p.Cys1055= (c.3165T>C) is absent from gnomAD v4.1 (gnomAD).

BLM p.Cys1055=

c.3165T>C · rs2505525552 · VCV1728361

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	donor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.7	GERP 2.5, phastCons 1
Overall
CADD	9.422	PHRED · no single calibrated threshold — expert panels disagree

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.Cys1055=
Coding: c.3165T>C
MANE Select: NM_000057
dbSNP: rs2505525552
Type: single nucleotide variant
Location: chr15:90794312 (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 1055: a UniProt-annotated variant site (in blm); 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

Similar variants

BLM p.Cys1055Arg Likely pathogenic ★★ same residue
BLM p.Cys1055Ser Pathogenic/Likely pathogenic ★★ same residue
BLM p.Cys1055Gly Likely pathogenic ★ same residue
BLM p.Cys1055Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
BLM c.2075-1G>A Likely pathogenic ★★ same condition
BLM c.2193+1G>A Pathogenic/Likely pathogenic ★★ same condition
BLM c.2308-2A>G Pathogenic/Likely pathogenic ★★ same condition
BLM c.2407-2A>G 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-cys1055 (accessed [today's date]).

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