Is BLM p.Ala1169Val (c.3506C>T) pathogenic?

BLM p.Ala1169Val (c.3506C>T) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-22). AlphaMissense: ambiguous (0.4804); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ala1169Val (c.3506C>T)?

BLM p.Ala1169Val (c.3506C>T) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Ala1169Val (c.3506C>T) in the general population?

BLM p.Ala1169Val (c.3506C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BLM p.Ala1169Val (c.3506C>T)?

AlphaMissense predicts ambiguous (score 0.4804) — an in-silico prediction, not a clinical call.

BLM p.Ala1169Val

c.3506C>T · rs2505547587 · VCV1732115

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4804 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4804	ambiguous
REVEL	0.299	indeterminate
SaProt	LLR -9.24	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	21.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BLM
Protein: p.Ala1169Val
Coding: c.3506C>T
MANE Select: NM_000057
dbSNP: rs2505547587
Type: single nucleotide variant
Location: chr15:90803668 (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 1169: a β-strand

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.Ala1169Ser Uncertain significance ★ ⚠ same residue
BLM p.Ala1169Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BLM p.Ala1169= Likely benign ★ same residue
BLM p.Ala1169fs Likely 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

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-ala1169val (accessed [today's date]).

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