Is BLM p.Arg899Gly (c.2695C>G) pathogenic?

BLM p.Arg899Gly (c.2695C>G) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-03-06). AlphaMissense: ambiguous (0.403); Very rare (popmax 0.000169%, nfe); Associated with Bloom syndrome.

What condition is associated with BLM p.Arg899Gly (c.2695C>G)?

BLM p.Arg899Gly (c.2695C>G) is associated with Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Arg899Gly (c.2695C>G) in the general population?

BLM p.Arg899Gly (c.2695C>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

How is Bloom syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BLM p.Arg899Gly (c.2695C>G)?

AlphaMissense predicts ambiguous (score 0.403) — an in-silico prediction, not a clinical call.

BLM p.Arg899Gly

c.2695C>G · rs587779884 · VCV1465439

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.403 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Bloom syndrome

Computational evidence

Protein change
AlphaMissense	0.403	ambiguous
REVEL	0.098	moderately benign-leaning
SaProt	LLR -8.57	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.45	GERP -4, phastCons 0.99
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	17.24	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,980 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,816 alleles · very rare

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.Arg899Gly
Coding: c.2695C>G
MANE Select: NM_000057
dbSNP: rs587779884
Type: single nucleotide variant
Location: chr15:90784953 (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 899: the '3' overhang dna-binding' region; an α-helix; the helicase c-terminal domain

Full BLM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bloom syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Bloom syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BLM p.Arg899Ter Pathogenic ★★ same residue
BLM p.Arg899Gln Uncertain significance ★★ ⚠ same residue
BLM p.Arg899= 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

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-arg899gly (accessed [today's date]).

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