Is BLM p.Asn268Ser (c.803A>G) pathogenic?

BLM p.Asn268Ser (c.803A>G) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-05). AlphaMissense: likely benign (0.0642); Ultra-rare (popmax 0.0112%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Asn268Ser (c.803A>G)?

BLM p.Asn268Ser (c.803A>G) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Asn268Ser (c.803A>G) in the general population?

BLM p.Asn268Ser (c.803A>G) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about BLM p.Asn268Ser (c.803A>G)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

BLM p.Asn268Ser

c.803A>G · rs763432949 · VCV578849

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.36	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 4.5	GERP 0.18, phastCons 0.8
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	14.05	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0112% East Asian · 5/44,818 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00118% 19/1,610,918 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,964
South Asian	0.00769%	12,999
African / African-American	0.00134%	74,872
European (non-Finnish)	0.00051%	196,239

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.Asn268Ser
Coding: c.803A>G
MANE Select: NM_000057
dbSNP: rs763432949
Type: single nucleotide variant
Location: chr15:90751790 (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 268: the 'disordered' region

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.Asn268Asp Uncertain significance ★ ⚠ same residue
BLM p.Asn268Tyr Uncertain significance ★ ⚠ same residue
BLM p.Asn268= Likely benign ★ same residue
BLM p.Asn268fs 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-asn268ser (accessed [today's date]).

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