Is BLK p.Ser110= (c.330T>C) pathogenic?

BLK p.Ser110= (c.330T>C) is classified Benign in BLK (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 52.7%, mid) — too common for a highly-penetrant pathogenic allele; Associated with systemic lupus erythematosus.

What condition is associated with BLK p.Ser110= (c.330T>C)?

BLK p.Ser110= (c.330T>C) is associated with systemic lupus erythematosus, maturity-onset diabetes of the young type 11 (ClinVar).

How is Systemic lupus erythematosus inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

BLK p.Ser110=

Q: How common is BLK p.Ser110= (c.330T>C) in the general population?

BLK p.Ser110= (c.330T>C) is common (popmax 52.7%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.330T>C · rs3816668 · VCV128527

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 52.7%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

systemic lupus erythematosus

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.52	GERP 1, phastCons 1
Overall
CADD	11.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 52.7% Middle Eastern · 3,193/6,058 alleles

Filtering AF 52.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 51.9%

Overall 48.6% 782,400/1,609,686 alleles · common exomes 708,594/1,457,678 · genomes 73,806/152,008 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	62.3%	2
Middle Easterngrpmax	52.7%	2
African / African-American	52.5%	2
European (non-Finnish)	50.8%	2
Remaining individualsnot grpmax-eligible	48.3%	2
South Asian	46.6%	2
Finnishnot grpmax-eligible	42.1%	2
Admixed American	35.9%	3
Amishnot grpmax-eligible	35.1%	3
East Asian	6.74%	15

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BLK
Protein: p.Ser110=
Coding: c.330T>C
MANE Select: NM_001715
dbSNP: rs3816668
Type: single nucleotide variant
Location: chr8:11549084 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89
Residue 110: the sh3 domain

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

Disease context

systemic lupus erythematosus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: maturity-onset diabetes of the young type 11

For Systemic lupus erythematosus (Orphanet):

Inheritance: Not applicable
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-5 / 10 000 (France)

Similar variants

BLK p.Ser110Asn Uncertain significance ★ ⚠ same residue
BLK p.Arg131Gln Uncertain significance ★★ ⚠ same condition
BLK p.Arg180His Uncertain significance ★★ ⚠ same condition
BLK p.Arg295Trp Uncertain significance ★★ same condition
BLK p.Arg298Gln Uncertain significance ★★ ⚠ same condition
BLK p.Gln226Pro Uncertain significance ★★ ⚠ same condition
BLK p.Gly451Ser Uncertain significance ★★ ⚠ same condition
BLK p.His55Arg Uncertain significance ★★ ⚠ 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/blk-p-ser110 (accessed [today's date]).

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