Is BLM p.Ala1043Asp (c.3128C>A) pathogenic?

BLM p.Ala1043Asp (c.3128C>A) is classified Benign/Likely benign in BLM (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-04). AlphaMissense: likely pathogenic (0.5779); Low-frequency (popmax 1.19%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ala1043Asp (c.3128C>A)?

BLM p.Ala1043Asp (c.3128C>A) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Ala1043Asp (c.3128C>A) in the general population?

BLM p.Ala1043Asp (c.3128C>A) is low-frequency (popmax 1.19%, afr) (gnomAD).

What do computational predictors say about BLM p.Ala1043Asp (c.3128C>A)?

AlphaMissense predicts likely pathogenic (score 0.5779) — an in-silico prediction, not a clinical call.

BLM p.Ala1043Asp

c.3128C>A · rs2229035 · VCV136516

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

AlphaMissense

likely pathogenic

0.5779 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.19%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5779	likely pathogenic
REVEL	0.345	indeterminate
SaProt	LLR -6.15	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic
Overall
CADD	24.3	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 1.19% African / African-American · 891/74,898 alleles

Filtering AF 1.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1%

Overall 0.0665% 1,068/1,606,918 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.19%	84
Admixed American	0.159%	628
Middle Eastern	0.116%	863
Remaining individualsnot grpmax-eligible	0.095%	1,053
European (non-Finnish)	0.00136%	73,507

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.Ala1043Asp
Coding: c.3128C>A
MANE Select: NM_000057
dbSNP: rs2229035
Type: single nucleotide variant
Location: chr15:90794275 (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 1043: a UniProt-annotated variant site (in); an α-helix

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.Ala1043Val Uncertain significance ★★ ⚠ same residue
BLM p.Ala1043= 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
BLM c.1882+2T>C Likely pathogenic ★★ same condition
BLM c.2074+1G>T 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-ala1043asp (accessed [today's date]).

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