Is BLM p.Asp983Val (c.2948A>T) pathogenic?

BLM p.Asp983Val (c.2948A>T) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-12-01). AlphaMissense: likely pathogenic (0.9921); Very rare (popmax 0.000339%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Asp983Val (c.2948A>T)?

BLM p.Asp983Val (c.2948A>T) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Asp983Val (c.2948A>T) in the general population?

BLM p.Asp983Val (c.2948A>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about BLM p.Asp983Val (c.2948A>T)?

AlphaMissense predicts likely pathogenic (score 0.9921) — an in-silico prediction, not a clinical call.

BLM p.Asp983Val

c.2948A>T · rs1896886266 · VCV844060

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9921 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9921	likely pathogenic · top 4% in BLM
REVEL	0.948	strongly pathogenic-leaning
SaProt	LLR -14.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.99 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	29.6	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

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,018 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,126 alleles · very rare exomes 4/1,461,862 · genomes 0/152,264 · joint denominator

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.Asp983Val
Coding: c.2948A>T
MANE Select: NM_000057
dbSNP: rs1896886266
Type: single nucleotide variant
Location: chr15:90790773 (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 983: a turn; 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

Also linked: Bloom syndrome

Similar variants

BLM p.Asp983Tyr Uncertain significance ★★ ⚠ same residue
BLM p.Asp983= Likely benign ★★ same residue
BLM p.Asp983His 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

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-asp983val (accessed [today's date]).

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