Is BLM p.Val970Gly (c.2909T>G) pathogenic?

BLM p.Val970Gly (c.2909T>G) is classified Uncertain significance in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-12). AlphaMissense: likely pathogenic (0.8439); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Val970Gly (c.2909T>G)?

BLM p.Val970Gly (c.2909T>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Val970Gly (c.2909T>G) in the general population?

BLM p.Val970Gly (c.2909T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BLM p.Val970Gly (c.2909T>G)?

AlphaMissense predicts likely pathogenic (score 0.8439) — an in-silico prediction, not a clinical call.

BLM p.Val970Gly

c.2909T>G · rs2505516443 · VCV2452563

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8439 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.8439	likely pathogenic
REVEL	0.765	pathogenic-leaning
SaProt	LLR -13.92	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Val970Gly
Coding: c.2909T>G
MANE Select: NM_000057
dbSNP: rs2505516443
Type: single nucleotide variant
Location: chr15:90790734 (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 970: an α-helix; the helicase c-terminal domain

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

Similar variants

BLM p.Val970Leu Uncertain significance ★★ ⚠ same residue
BLM p.Val970= Likely benign ★ same residue
BLM c.2075-1G>A Likely pathogenic ★★ same condition
BLM c.2193+1G>A Pathogenic/Likely pathogenic ★★ same condition
BLM c.2308-2A>G Pathogenic/Likely pathogenic ★★ same condition
BLM c.2407-2A>G Likely pathogenic ★★ same condition
BLM c.2555+1G>A Likely pathogenic ★★ same condition
BLM c.2556-2A>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-val970gly (accessed [today's date]).

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