Is BLK p.Arg115Ter (c.343C>T) pathogenic?

BLK p.Arg115Ter (c.343C>T) is classified Uncertain significance in BLK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-19). Ultra-rare (popmax 0.0134%, sas).

How common is BLK p.Arg115Ter (c.343C>T) in the general population?

BLK p.Arg115Ter (c.343C>T) is ultra-rare (popmax 0.0134%, sas) (gnomAD).

BLK p.Arg115Ter

c.343C>T · rs754227902 · VCV4711699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -3.9, phastCons 0.028
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% South Asian · 12/89,516 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00602%

Overall 0.00273% 44/1,609,310 alleles · ultra-rare exomes 41/1,457,150 · genomes 3/152,160 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0134%	7,460
Remaining individualsnot grpmax-eligible	0.00642%	15,587
European (non-Finnish)	0.00229%	43,632
Admixed American	0.00168%	59,446

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.Arg115Ter
Coding: c.343C>T
MANE Select: NM_001715
dbSNP: rs754227902
Type: single nucleotide variant
Location: chr8:11549097 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89
Residue 115: the sh3 domain

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

Similar variants

BLK p.Arg115Gln Uncertain significance ★ ⚠ same residue
BLK p.Arg131Gln Uncertain significance ★★ ⚠ same type
BLK p.Arg180His Uncertain significance ★★ ⚠ same type
BLK p.Arg238Trp Uncertain significance ★★ ⚠ same type
BLK p.Arg295Trp Uncertain significance ★★ same type
BLK p.Arg298Gln Uncertain significance ★★ ⚠ same type
BLK p.Arg466His Uncertain significance ★★ ⚠ same type
BLK p.Asp68Val Uncertain significance ★★ same type

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-arg115ter (accessed [today's date]).

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