Is BLM p.Lys323Arg (c.968A>G) pathogenic?

BLM p.Lys323Arg (c.968A>G) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 18 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0814); Rare (popmax 0.115%, nfe); Associated with Hereditary cancer.

What condition is associated with BLM p.Lys323Arg (c.968A>G)?

BLM p.Lys323Arg (c.968A>G) is associated with Hereditary cancer, Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Lys323Arg (c.968A>G) in the general population?

BLM p.Lys323Arg (c.968A>G) is rare (popmax 0.115%, nfe) (gnomAD).

What do computational predictors say about BLM p.Lys323Arg (c.968A>G)?

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

BLM p.Lys323Arg

c.968A>G · rs146504061 · VCV127518

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 18 submitters

AlphaMissense

likely benign

0.0814 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Hereditary cancer

Computational evidence

Protein change
AlphaMissense	0.0814	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -7.31	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 5.3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	18.12	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 0.115% European (non-Finnish) · 1,361/1,179,872 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.0893% 1,441/1,613,702 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.115%	867
Remaining individualsnot grpmax-eligible	0.088%	1,136
African / African-American	0.0214%	4,683
Admixed American	0.0117%	8,567
Finnishnot grpmax-eligible	0.00156%	63,946
South Asian	0.0011%	91,042

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.Lys323Arg
Coding: c.968A>G
MANE Select: NM_000057
dbSNP: rs146504061
Type: single nucleotide variant
Location: chr15:90754819 (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 323: the 'necessary for interaction with spidr' region

Full BLM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hereditary cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bloom syndrome hereditary neoplastic syndrome

Similar variants

BLM p.Lys323Gln 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
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
BLM c.2075-1G>A 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-lys323arg (accessed [today's date]).

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