Is BLM p.Ile593Val (c.1777A>G) pathogenic?

BLM p.Ile593Val (c.1777A>G) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-05-09). AlphaMissense: likely benign (0.0538); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ile593Val (c.1777A>G)?

BLM p.Ile593Val (c.1777A>G) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Ile593Val (c.1777A>G) in the general population?

BLM p.Ile593Val (c.1777A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BLM p.Ile593Val (c.1777A>G)?

AlphaMissense predicts likely benign (score 0.0538) — an in-silico prediction, not a clinical call.

BLM p.Ile593Val

c.1777A>G · rs2505429011 · VCV1779894

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0538 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,531,672)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0538	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -5.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -5.4
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	0.061	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

No allele count reported in gnomAD v4.1 (AN 1,531,672). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BLM
Protein: p.Ile593Val
Coding: c.1777A>G
MANE Select: NM_000057
dbSNP: rs2505429011
Type: single nucleotide variant
Location: chr15:90761150 (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 593: the 'necessary for interaction with spidr' 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.Ile593Leu Uncertain significance ★ ⚠ same residue
BLM p.Ile593Thr 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
BLM c.2074+1G>T 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-ile593val (accessed [today's date]).

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