Is BLM p.Tyr784Asn (c.2350T>A) pathogenic?

BLM p.Tyr784Asn (c.2350T>A) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-13). AlphaMissense: likely benign (0.3083); Very rare (popmax 0.00446%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Tyr784Asn (c.2350T>A)?

BLM p.Tyr784Asn (c.2350T>A) is associated with hereditary neoplastic syndrome, ovarian cancer, Bloom syndrome (ClinVar).

How common is BLM p.Tyr784Asn (c.2350T>A) in the general population?

BLM p.Tyr784Asn (c.2350T>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about BLM p.Tyr784Asn (c.2350T>A)?

AlphaMissense predicts likely benign (score 0.3083) — an in-silico prediction, not a clinical call.

BLM p.Tyr784Asn

c.2350T>A · rs779746222 · VCV821139

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.3083 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.3083	likely benign
REVEL	0.403	indeterminate
SaProt	LLR -11.29	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	24.6	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 0.00446% East Asian · 2/44,880 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000137% 2/1,461,348 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.Tyr784Asn
Coding: c.2350T>A
MANE Select: NM_000057
dbSNP: rs779746222
Type: single nucleotide variant
Location: chr15:90769175 (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 784: the helicase atp-binding domain; an α-helix

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: ovarian cancer Bloom syndrome

Similar variants

BLM p.Tyr784Cys Uncertain significance ★★ ⚠ same residue
BLM p.Tyr784His Uncertain significance ★★ ⚠ same residue
BLM p.Tyr784Phe Uncertain significance ★★ ⚠ same residue
BLM p.Tyr784= Likely benign ★★ same residue
BLM p.Tyr784Ter Pathogenic ★ same residue
BLM p.Tyr784fs Likely pathogenic 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-tyr784asn (accessed [today's date]).

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