Is BLM p.Lys272= (c.816G>A) pathogenic?

BLM p.Lys272= (c.816G>A) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-28). Rare (popmax 0.14%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Lys272= (c.816G>A)?

BLM p.Lys272= (c.816G>A) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Lys272= (c.816G>A) in the general population?

BLM p.Lys272= (c.816G>A) is rare (popmax 0.14%, afr) (gnomAD).

BLM p.Lys272=

c.816G>A · rs139295905 · VCV454166

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.14%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -2.4, phastCons 1
Overall
CADD	8.353	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.14% African / African-American · 105/75,026 alleles

Filtering AF 0.118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.11%

Overall 0.0072% 116/1,612,170 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.14%	715
Remaining individualsnot grpmax-eligible	0.0128%	7,806
Admixed American	0.00333%	30,000
South Asian	0.0011%	91,020

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.Lys272=
Coding: c.816G>A
MANE Select: NM_000057
dbSNP: rs139295905
Type: single nucleotide variant
Location: chr15:90751803 (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 272: the 'disordered' region

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.Lys272Arg Uncertain significance ★★ ⚠ same residue
BLM p.Lys272Ter Pathogenic ★ same residue
BLM p.Lys272Gln Uncertain significance ★ ⚠ same residue
BLM p.Lys272_Lys273del 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

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-lys272 (accessed [today's date]).

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