Is BLM p.Ser1092Arg (c.3276T>A) pathogenic?

BLM p.Ser1092Arg (c.3276T>A) is classified Uncertain significance in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). AlphaMissense: ambiguous (0.4046); Ultra-rare (popmax 0.0165%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ser1092Arg (c.3276T>A)?

BLM p.Ser1092Arg (c.3276T>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Ser1092Arg (c.3276T>A) in the general population?

BLM p.Ser1092Arg (c.3276T>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about BLM p.Ser1092Arg (c.3276T>A)?

AlphaMissense predicts ambiguous (score 0.4046) — an in-silico prediction, not a clinical call.

BLM p.Ser1092Arg

c.3276T>A · rs756576705 · VCV1729676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4046 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4046	ambiguous
REVEL	0.158	moderately benign-leaning
SaProt	LLR -7.46	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 0.46	GERP 0.23, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	19.79	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 0.0165% Middle Eastern · 1/6,050 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.00031% 5/1,611,842 alleles · ultra-rare exomes 5/1,459,496 · genomes 0/152,346 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,050
South Asian	0.0044%	22,739

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.Ser1092Arg
Coding: c.3276T>A
MANE Select: NM_000057
dbSNP: rs756576705
Type: single nucleotide variant
Location: chr15:90798255 (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

Similar variants

BLM p.Ser1092Asn Uncertain significance ★★ ⚠ 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
BLM c.2662+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-ser1092arg (accessed [today's date]).

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