Is BLM p.Ala833Val (c.2498C>T) pathogenic?

BLM p.Ala833Val (c.2498C>T) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-06-18). AlphaMissense: likely pathogenic (0.9684); Absent from gnomAD v4.1; Associated with ovarian cancer.

What condition is associated with BLM p.Ala833Val (c.2498C>T)?

BLM p.Ala833Val (c.2498C>T) is associated with ovarian cancer, Bloom syndrome (ClinVar).

How common is BLM p.Ala833Val (c.2498C>T) in the general population?

BLM p.Ala833Val (c.2498C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BLM p.Ala833Val (c.2498C>T)?

AlphaMissense predicts likely pathogenic (score 0.9684) — an in-silico prediction, not a clinical call.

BLM p.Ala833Val

c.2498C>T · rs2505456977 · VCV2445358

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9684 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.9684	likely pathogenic · top 9% in BLM
REVEL	0.574	indeterminate
SaProt	LLR -14.34	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.69 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	28.6	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.Ala833Val
Coding: c.2498C>T
MANE Select: NM_000057
dbSNP: rs2505456977
Type: single nucleotide variant
Location: chr15:90769529 (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 833: the helicase atp-binding domain

Full BLM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bloom syndrome

Similar variants

BLM p.Ala833Gly Uncertain significance ★★ ⚠ same residue
BLM p.Ala833Thr Uncertain significance ★★ ⚠ same residue
BLM p.Ala833= Likely benign ★ 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-ala833val (accessed [today's date]).

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