Is BLM p.Asp239His (c.715G>C) pathogenic?

BLM p.Asp239His (c.715G>C) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1452); Rare (popmax 0.167%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Asp239His (c.715G>C)?

BLM p.Asp239His (c.715G>C) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Asp239His (c.715G>C) in the general population?

BLM p.Asp239His (c.715G>C) is rare (popmax 0.167%, eas) (gnomAD).

What do computational predictors say about BLM p.Asp239His (c.715G>C)?

AlphaMissense predicts likely benign (score 0.1452) — an in-silico prediction, not a clinical call.

BLM p.Asp239His

c.715G>C · rs200756519 · VCV454163

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1452 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.167%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1452	likely benign
REVEL	0.136	moderately benign-leaning
SaProt	LLR -10.35	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP -0.27, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	21.7	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 0.167% East Asian · 75/44,888 alleles

Filtering AF 0.137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.125%

Overall 0.00477% 77/1,614,202 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.167%	599
Remaining individualsnot grpmax-eligible	0.0016%	62,506
African / African-American	0.00133%	75,062

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.Asp239His
Coding: c.715G>C
MANE Select: NM_000057
dbSNP: rs200756519
Type: single nucleotide variant
Location: chr15:90749983 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 61.10 · 16 PDB

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: hereditary breast ovarian cancer syndrome Bloom syndrome

Similar variants

BLM p.Asp239Ala Uncertain significance ★★ ⚠ same residue
BLM p.Asp239Asn Uncertain significance ★★ ⚠ same residue
BLM p.Asp239Gly Uncertain significance ★★ ⚠ same residue
BLM p.Asp239Val Uncertain significance ★★ ⚠ same residue
BLM p.Asp239= Likely benign ★★ same residue
BLM p.Asp239Glu Uncertain significance ★ ⚠ same residue
BLM c.1087+1G>A Likely pathogenic ★★ same condition
BLM c.1088-1G>A 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-asp239his (accessed [today's date]).

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