Is BLM p.Ser622Ter (c.1865C>G) pathogenic?

BLM p.Ser622Ter (c.1865C>G) is classified Pathogenic/Likely pathogenic in BLM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-16). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ser622Ter (c.1865C>G)?

BLM p.Ser622Ter (c.1865C>G) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Ser622Ter (c.1865C>G) in the general population?

BLM p.Ser622Ter (c.1865C>G) is absent from gnomAD v4.1 (gnomAD).

BLM p.Ser622Ter

c.1865C>G · rs2505429817 · VCV1781570

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,534,874)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 2.5, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,534,874). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BLM
Protein: p.Ser622Ter
Coding: c.1865C>G
MANE Select: NM_000057
dbSNP: rs2505429817
Type: single nucleotide variant
Location: chr15:90761238 (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.Ser622Ala Uncertain significance ★★ ⚠ same residue
BLM p.Ser622Leu Uncertain significance ★★ ⚠ same residue
BLM p.Ser622Pro Uncertain significance ★★ ⚠ same residue
BLM p.Ser622= Likely benign ★★ same residue
BLM p.Ser622fs 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

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-ser622ter (accessed [today's date]).

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