Is BLM p.Ala1203Val (c.3608C>T) pathogenic?

BLM p.Ala1203Val (c.3608C>T) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-18). AlphaMissense: likely benign (0.0808); Very rare (popmax 0.00329%, sas); Associated with Bloom syndrome.

What condition is associated with BLM p.Ala1203Val (c.3608C>T)?

BLM p.Ala1203Val (c.3608C>T) is associated with Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Ala1203Val (c.3608C>T) in the general population?

BLM p.Ala1203Val (c.3608C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

How is Bloom syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BLM p.Ala1203Val (c.3608C>T)?

AlphaMissense predicts likely benign (score 0.0808) — an in-silico prediction, not a clinical call.

BLM p.Ala1203Val

c.3608C>T · rs757088548 · VCV485332

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0808 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bloom syndrome

Computational evidence

Protein change
AlphaMissense	0.0808	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -6.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	24.1	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 0.00329% South Asian · 3/91,086 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00192% 31/1,613,878 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,362
Remaining individualsnot grpmax-eligible	0.0032%	31,242
East Asian	0.00223%	44,886
European (non-Finnish)	0.00212%	47,198

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.Ala1203Val
Coding: c.3608C>T
MANE Select: NM_000057
dbSNP: rs757088548
Type: single nucleotide variant
Location: chr15:90804216 (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

Bloom syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Bloom syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BLM p.Ala1203Thr Uncertain significance ★★ ⚠ same residue
BLM p.Ala1203= Likely benign ★★ same residue
BLM p.Ala1203Gly Uncertain significance ★ ⚠ same residue
BLM p.Ala1203Pro Uncertain significance ★ ⚠ same residue
BLM p.Ala1203_Leu1204insTer 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-ala1203val (accessed [today's date]).

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