Is BLM p.Pro868= (c.2604G>A) pathogenic?

BLM p.Pro868= (c.2604G>A) is classified Likely benign in BLM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-18). Very rare (popmax 0.00534%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Pro868= (c.2604G>A)?

BLM p.Pro868= (c.2604G>A) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Pro868= (c.2604G>A) in the general population?

BLM p.Pro868= (c.2604G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

BLM p.Pro868=

c.2604G>A · rs768447097 · VCV236805

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.27	acceptor loss, 48 bp away · masked 0 · deltas
Pangolin	Δ0.25	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -4.8	GERP -5.2
Overall
CADD	0.574	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,902 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000744% 12/1,613,722 alleles · very rare exomes 10/1,461,604 · genomes 2/152,118 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,726
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)	0.000593%	168,545

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.Pro868=
Coding: c.2604G>A
MANE Select: NM_000057
dbSNP: rs768447097
Type: single nucleotide variant
Location: chr15:90782870 (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 868: a β-strand; a UniProt-annotated variant site (in)

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.Pro868Arg Uncertain significance ★★ ⚠ same residue
BLM p.Pro868Leu Benign/Likely benign ★★ ⚠ same residue
BLM p.Pro868Gln Uncertain significance ★ ⚠ same residue
BLM p.Pro868_Lys869delinsLeuGlu Benign ★ same residue
BLM p.Pro868fs 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

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-pro868 (accessed [today's date]).

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