Is BLM p.Phe160Ser (c.479T>C) pathogenic?

BLM p.Phe160Ser (c.479T>C) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-17). AlphaMissense: ambiguous (0.5238); Very rare (popmax 0.00266%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Phe160Ser (c.479T>C)?

BLM p.Phe160Ser (c.479T>C) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Phe160Ser (c.479T>C) in the general population?

BLM p.Phe160Ser (c.479T>C) is very rare (popmax 0.00266%, afr) (gnomAD).

What do computational predictors say about BLM p.Phe160Ser (c.479T>C)?

AlphaMissense predicts ambiguous (score 0.5238) — an in-silico prediction, not a clinical call.

BLM p.Phe160Ser

c.479T>C · rs147084654 · VCV1743170

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5238 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00266%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5238	ambiguous
REVEL	0.485	indeterminate
SaProt	LLR -6.30	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	26.0	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 0.00266% African / African-American · 2/75,064 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,614,156 alleles · very rare exomes 1/1,461,776 · genomes 3/152,380 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00266%	37,532
East Asian	0.00223%	44,888
European (non-Finnish)	8.47e-05%	1,179,981

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.Phe160Ser
Coding: c.479T>C
MANE Select: NM_000057
dbSNP: rs147084654
Type: single nucleotide variant
Location: chr15:90749747 (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: Bloom syndrome

Similar variants

BLM p.Phe160= Likely benign ★★ same residue
BLM p.Phe160Cys 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-phe160ser (accessed [today's date]).

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