Is BLM p.Ser1368Thr (c.4102T>A) pathogenic?

BLM p.Ser1368Thr (c.4102T>A) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-19). AlphaMissense: likely benign (0.0694); Very rare (popmax 0.00934%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ser1368Thr (c.4102T>A)?

BLM p.Ser1368Thr (c.4102T>A) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Ser1368Thr (c.4102T>A) in the general population?

BLM p.Ser1368Thr (c.4102T>A) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about BLM p.Ser1368Thr (c.4102T>A)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

BLM p.Ser1368Thr

c.4102T>A · rs587778104 · VCV1017651

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -6.98	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 0.11	GERP -4.9, phastCons 0.038
Regional constraint	o/e 0.88	unconstrained · MANE · 6,066 bp · p 0.12 · regional, not allelic
Overall
CADD	1.808	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 0.00934% African / African-American · 7/74,916 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000558% 9/1,614,042 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,702
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	8.47e-05%	1,180,048

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.Ser1368Thr
Coding: c.4102T>A
MANE Select: NM_000057
dbSNP: rs587778104
Type: single nucleotide variant
Location: chr15:90815127 (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 1368: 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.Ser1368Cys Uncertain significance ★★ ⚠ same residue
BLM p.Ser1368= Likely benign ★★ same residue
BLM p.Ser1368Pro Conflicting classifications of pathogenicity ★ ⚠ 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

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-ser1368thr (accessed [today's date]).

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