Is BLM p.Arg1016Thr (c.3047G>C) pathogenic?

BLM p.Arg1016Thr (c.3047G>C) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-02-23). AlphaMissense: ambiguous (0.3499); Very rare (popmax 8.51e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Arg1016Thr (c.3047G>C)?

BLM p.Arg1016Thr (c.3047G>C) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Arg1016Thr (c.3047G>C) in the general population?

BLM p.Arg1016Thr (c.3047G>C) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about BLM p.Arg1016Thr (c.3047G>C)?

AlphaMissense predicts ambiguous (score 0.3499) — an in-silico prediction, not a clinical call.

BLM p.Arg1016Thr

c.3047G>C · rs2151187181 · VCV1683324

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3499 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.3499	ambiguous
REVEL	0.183	benign-leaning
SaProt	LLR -5.49	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.48	GERP -4.8, phastCons 0.002
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	13.1	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 8.51e-05% European (non-Finnish) · 1/1,174,434 alleles

Overall 6.88e-05% 1/1,452,838 alleles · very rare

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.Arg1016Thr
Coding: c.3047G>C
MANE Select: NM_000057
dbSNP: rs2151187181
Type: single nucleotide variant
Location: chr15:90794194 (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 1016: 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

Also linked: Bloom syndrome

Similar variants

BLM p.Arg1016Gly Uncertain significance ★ ⚠ same residue
BLM p.Arg1016Lys Uncertain significance ★ ⚠ same residue
BLM p.Arg1016= 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-arg1016thr (accessed [today's date]).

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