Is BLM p.Ser987Phe (c.2960C>T) pathogenic?

BLM p.Ser987Phe (c.2960C>T) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-13). AlphaMissense: likely pathogenic (0.9891); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ser987Phe (c.2960C>T)?

BLM p.Ser987Phe (c.2960C>T) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Ser987Phe (c.2960C>T) in the general population?

BLM p.Ser987Phe (c.2960C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BLM p.Ser987Phe (c.2960C>T)?

AlphaMissense predicts likely pathogenic (score 0.9891) — an in-silico prediction, not a clinical call.

BLM p.Ser987Phe

c.2960C>T · rs1555423111 · VCV454123

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9891 · 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	0.9891	likely pathogenic · top 5% in BLM
REVEL	0.923	moderately pathogenic-leaning
SaProt	LLR -16.39	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	28.3	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.Ser987Phe
Coding: c.2960C>T
MANE Select: NM_000057
dbSNP: rs1555423111
Type: single nucleotide variant
Location: chr15:90790785 (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 987: a β-strand; 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

Also linked: Bloom syndrome

Similar variants

BLM p.Ser987Cys Uncertain significance ★ ⚠ same residue
BLM p.Ser987= Likely benign ★ 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-ser987phe (accessed [today's date]).

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