Is BLM p.Lys38= (c.114A>G) pathogenic?

BLM p.Lys38= (c.114A>G) is classified Benign/Likely benign in BLM (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0134%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Lys38= (c.114A>G)?

BLM p.Lys38= (c.114A>G) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Lys38= (c.114A>G) in the general population?

BLM p.Lys38= (c.114A>G) is ultra-rare (popmax 0.0134%, amr) (gnomAD).

BLM p.Lys38=

c.114A>G · rs770017301 · VCV454066

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, amr)

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 1.5	GERP -3.5, phastCons 1
Overall
CADD	7.625	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% Admixed American · 8/59,536 alleles

Filtering AF 0.00666% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00486%

Overall 0.00449% 72/1,604,044 alleles · ultra-rare exomes 63/1,451,824 · genomes 9/152,220 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0134%	7,442
Remaining individualsnot grpmax-eligible	0.00805%	12,420
European (non-Finnish)	0.00461%	21,707
African / African-American	0.00402%	24,849
Finnishnot grpmax-eligible	0.00313%	31,990

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.Lys38=
Coding: c.114A>G
MANE Select: NM_000057
dbSNP: rs770017301
Type: single nucleotide variant
Location: chr15:90749382 (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 38: a cross-link site

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.Lys38Thr Uncertain significance ★★ ⚠ same residue
BLM p.Lys38Arg Uncertain significance ★ ⚠ same residue
BLM p.Lys38Glu 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-lys38 (accessed [today's date]).

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