Is BLM p.Asp64Val (c.191A>T) pathogenic?

BLM p.Asp64Val (c.191A>T) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 15 submitters; last evaluated 2026-03-24). AlphaMissense: likely benign (0.1846); Ultra-rare (popmax 0.0546%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Asp64Val (c.191A>T)?

BLM p.Asp64Val (c.191A>T) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Asp64Val (c.191A>T) in the general population?

BLM p.Asp64Val (c.191A>T) is ultra-rare (popmax 0.0546%, nfe) (gnomAD).

What do computational predictors say about BLM p.Asp64Val (c.191A>T)?

AlphaMissense predicts likely benign (score 0.1846) — an in-silico prediction, not a clinical call.

BLM p.Asp64Val

c.191A>T · rs140382474 · VCV127479

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 15 submitters

AlphaMissense

likely benign

0.1846 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0546%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1846	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.25, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	22.5	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 0.0546% European (non-Finnish) · 643/1,178,144 alleles

Filtering AF 0.0511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0497%

Overall 0.0416% 671/1,612,010 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0546%	1,832
Remaining individualsnot grpmax-eligible	0.032%	3,121
Middle Eastern	0.0164%	6,082
African / African-American	0.00534%	18,726
Admixed American	0.00167%	60,010
Finnishnot grpmax-eligible	0.00156%	64,036
South Asian	0.0011%	91,048

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.Asp64Val
Coding: c.191A>T
MANE Select: NM_000057
dbSNP: rs140382474
Type: single nucleotide variant
Location: chr15:90749459 (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.Asp64Ala Uncertain significance ★★ ⚠ same residue
BLM p.Asp64His Uncertain significance ★★ ⚠ same residue
BLM p.Asp64Tyr Uncertain significance ★★ ⚠ same residue
BLM p.Asp64= Likely benign ★ same residue
BLM p.Asp64Gly Uncertain significance ★ ⚠ 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-asp64val (accessed [today's date]).

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