Is BLM p.Arg85Thr (c.254G>C) pathogenic?

BLM p.Arg85Thr (c.254G>C) is classified Benign/Likely benign in BLM (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-06-30). AlphaMissense: likely benign (0.0604); Rare (popmax 0.664%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Arg85Thr (c.254G>C)?

BLM p.Arg85Thr (c.254G>C) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Arg85Thr (c.254G>C) in the general population?

BLM p.Arg85Thr (c.254G>C) is rare (popmax 0.664%, afr) (gnomAD).

What do computational predictors say about BLM p.Arg85Thr (c.254G>C)?

AlphaMissense predicts likely benign (score 0.0604) — an in-silico prediction, not a clinical call.

BLM p.Arg85Thr

c.254G>C · rs141503266 · VCV127488

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

AlphaMissense

likely benign

0.0604 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.664%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0604	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -4.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.046	GERP -5.1
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	0.191	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 0.664% African / African-American · 498/75,032 alleles

Filtering AF 0.616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.596%

Overall 0.0359% 579/1,614,124 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.664%	151
Admixed American	0.0783%	1,277
Remaining individualsnot grpmax-eligible	0.0416%	2,404
South Asian	0.0022%	45,536
European (non-Finnish)	0.000508%	196,672

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.Arg85Thr
Coding: c.254G>C
MANE Select: NM_000057
dbSNP: rs141503266
Type: single nucleotide variant
Location: chr15:90749522 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 61.10 · 16 PDB

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.Arg85= Likely benign ★★ same residue
BLM p.Arg85Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
BLM p.Arg85Ser Uncertain significance ⚠ same residue
BLM p.Arg85fs Pathogenic/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-arg85thr (accessed [today's date]).

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