Is BLM p.Val1205Ile (c.3613G>A) pathogenic?

BLM p.Val1205Ile (c.3613G>A) is classified Benign/Likely benign in BLM (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-06-12). AlphaMissense: likely benign (0.0814); Rare (popmax 0.705%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Val1205Ile (c.3613G>A)?

BLM p.Val1205Ile (c.3613G>A) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Val1205Ile (c.3613G>A) in the general population?

BLM p.Val1205Ile (c.3613G>A) is rare (popmax 0.705%, afr) (gnomAD).

What do computational predictors say about BLM p.Val1205Ile (c.3613G>A)?

AlphaMissense predicts likely benign (score 0.0814) — an in-silico prediction, not a clinical call.

BLM p.Val1205Ile

c.3613G>A · rs28385141 · VCV133701

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.0814 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.705%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0814	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -7.91	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 9.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	22.9	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 0.705% African / African-American · 529/75,038 alleles

Filtering AF 0.655% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.636%

Overall 0.0388% 626/1,614,150 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.705%	142
Admixed American	0.0866%	1,154
Remaining individualsnot grpmax-eligible	0.056%	1,786
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
European (non-Finnish)	0.000763%	131,111

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.Val1205Ile
Coding: c.3613G>A
MANE Select: NM_000057
dbSNP: rs28385141
Type: single nucleotide variant
Location: chr15:90804221 (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 1205: a UniProt-annotated variant site (in)

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.Val1205Ala Uncertain significance ★ ⚠ same residue
BLM p.Val1205Glu Uncertain significance ★ ⚠ same residue
BLM p.Val1205Leu Uncertain significance ★ ⚠ same residue
BLM p.Val1205= Likely benign ★ 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

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-val1205ile (accessed [today's date]).

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