Is BLM p.Phe193Leu (c.577T>C) pathogenic?

BLM p.Phe193Leu (c.577T>C) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-30). AlphaMissense: likely benign (0.2732); Very rare (popmax 0.00239%, nfe); Associated with Bloom syndrome.

What condition is associated with BLM p.Phe193Leu (c.577T>C)?

BLM p.Phe193Leu (c.577T>C) is associated with Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Phe193Leu (c.577T>C) in the general population?

BLM p.Phe193Leu (c.577T>C) is very rare (popmax 0.00239%, nfe) (gnomAD).

How is Bloom syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BLM p.Phe193Leu (c.577T>C)?

AlphaMissense predicts likely benign (score 0.2732) — an in-silico prediction, not a clinical call.

BLM p.Phe193Leu

c.577T>C · rs779348937 · VCV578232

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2732 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00239%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bloom syndrome

Computational evidence

Protein change
AlphaMissense	0.2732	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -4.64	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 -0.79	GERP -2.6, phastCons 0.002
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	7.945	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00239% European (non-Finnish) · 28/1,170,982 alleles

Filtering AF 0.00166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00143%

Overall 0.00182% 29/1,593,276 alleles · very rare exomes 28/1,441,062 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00239%	41,821
Finnishnot grpmax-eligible	0.00158%	63,318

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.Phe193Leu
Coding: c.577T>C
MANE Select: NM_000057
dbSNP: rs779348937
Type: single nucleotide variant
Location: chr15:90749845 (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

Bloom syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Bloom syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BLM p.Phe193Cys Uncertain significance ★★ ⚠ same residue
BLM p.Phe193= Likely benign ★ same residue
BLM p.Phe193_Phe194insTer Pathogenic ★★ 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-phe193leu (accessed [today's date]).

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