Is BLM p.Leu896Pro (c.2687T>C) pathogenic?

BLM p.Leu896Pro (c.2687T>C) is classified Uncertain significance in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-30). AlphaMissense: likely pathogenic (0.9881); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Leu896Pro (c.2687T>C)?

BLM p.Leu896Pro (c.2687T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Leu896Pro (c.2687T>C) in the general population?

BLM p.Leu896Pro (c.2687T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BLM p.Leu896Pro (c.2687T>C)?

AlphaMissense predicts likely pathogenic (score 0.9881) — an in-silico prediction, not a clinical call.

BLM p.Leu896Pro

c.2687T>C · rs2505501340 · VCV1794746

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9881 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9881	likely pathogenic · top 6% in BLM
REVEL	0.903	moderately pathogenic-leaning
SaProt	LLR -10.30	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.64 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	30.0	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

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.Leu896Pro
Coding: c.2687T>C
MANE Select: NM_000057
dbSNP: rs2505501340
Type: single nucleotide variant
Location: chr15:90784945 (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 896: the helicase c-terminal domain

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.Leu896Phe Uncertain significance ★★ same residue
BLM p.Leu896Val Uncertain significance ★★ ⚠ same residue
BLM p.Leu896= Likely benign ★ 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
BLM c.2555+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-leu896pro (accessed [today's date]).

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