Is BLM p.Ser316del (c.933TTC[2]) pathogenic?

BLM p.Ser316del (c.933TTC[2]) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ser316del (c.933TTC[2])?

BLM p.Ser316del (c.933TTC[2]) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Ser316del (c.933TTC[2]) in the general population?

BLM p.Ser316del (c.933TTC[2]) is very rare (popmax 0.0011%, sas) (gnomAD).

BLM p.Ser316del

c.933TTC[2] · rs564966225 · VCV576629

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 · substitutions only
Constraint at this position
Conservation	phyloP -1.5	GERP -5.6
Overall
CADD	7.088	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,046 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000496% 8/1,612,484 alleles · very rare exomes 5/1,460,414 · genomes 3/152,070 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,438
South Asiangrpmax	0.0011%	91,046
European (non-Finnish)	0.000509%	196,490

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser316del
Coding: c.933TTC[2]
MANE Select: NM_000057
dbSNP: rs564966225
Type: Microsatellite
Location: chr15:90751919 (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 316: the 'necessary for interaction with spidr' 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.Arg191fs Pathogenic ★★ same condition
BLM p.Asn202fs Pathogenic ★★ same condition
BLM p.Asn782fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Cys361_Asp362delinsTer Pathogenic ★★ same condition
BLM p.Gln100fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Gln802fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Leu1246fs Pathogenic ★★ same condition
BLM p.Leu258fs 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-ser316del (accessed [today's date]).

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