Is BLM p.Ile892Met (c.2676A>G) pathogenic?

BLM p.Ile892Met (c.2676A>G) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-26). AlphaMissense: likely pathogenic (0.7908); Ultra-rare (popmax 0.0165%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ile892Met (c.2676A>G)?

BLM p.Ile892Met (c.2676A>G) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Ile892Met (c.2676A>G) in the general population?

BLM p.Ile892Met (c.2676A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about BLM p.Ile892Met (c.2676A>G)?

AlphaMissense predicts likely pathogenic (score 0.7908) — an in-silico prediction, not a clinical call.

BLM p.Ile892Met

c.2676A>G · rs1284962627 · VCV2142789

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7908 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.7908	likely pathogenic
REVEL	0.755	pathogenic-leaning
SaProt	LLR -12.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.78	GERP -2.8, phastCons 0.97
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	23.4	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

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000124% 2/1,613,684 alleles · ultra-rare exomes 2/1,461,432 · genomes 0/152,252 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
East Asian	0.00223%	44,874

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.Ile892Met
Coding: c.2676A>G
MANE Select: NM_000057
dbSNP: rs1284962627
Type: single nucleotide variant
Location: chr15:90784934 (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 892: 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.Ile892Val Uncertain significance ★★ same residue
BLM p.Ile892Lys Uncertain significance ★ ⚠ same residue
BLM p.Ile892Thr Uncertain significance ★ ⚠ 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-ile892met (accessed [today's date]).

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