Is BLM p.Ser1062= (c.3186T>A) pathogenic?

BLM p.Ser1062= (c.3186T>A) is classified Likely benign in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-15). Very rare (popmax 0.00676%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ser1062= (c.3186T>A)?

BLM p.Ser1062= (c.3186T>A) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Ser1062= (c.3186T>A) in the general population?

BLM p.Ser1062= (c.3186T>A) is very rare (popmax 0.00676%, eas) (gnomAD).

BLM p.Ser1062=

c.3186T>A · rs774258877 · VCV1161622

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00676%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 1.5, phastCons 1
Overall
CADD	9.128	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00676% East Asian · 3/44,374 alleles

Filtering AF 0.00179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000897%

Overall 0.000375% 6/1,600,960 alleles · very rare exomes 6/1,448,666 · genomes 0/152,294 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00676%	14,791
Remaining individualsnot grpmax-eligible	0.00162%	61,918
European (non-Finnish)	0.00017%	587,165

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.Ser1062=
Coding: c.3186T>A
MANE Select: NM_000057
dbSNP: rs774258877
Type: single nucleotide variant
Location: chr15:90794333 (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.Ser1062Ala Uncertain significance ★ ⚠ same residue
BLM p.Ser1062Tyr 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
BLM c.2074+1G>T 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-ser1062 (accessed [today's date]).

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