Is BFSP2 p.Arg5Ter (c.13C>T) pathogenic?

BFSP2 p.Arg5Ter (c.13C>T) is classified Uncertain significance in BFSP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-26). Very rare (popmax 0.00271%, nfe); Associated with cataract 12 multiple types.

What condition is associated with BFSP2 p.Arg5Ter (c.13C>T)?

BFSP2 p.Arg5Ter (c.13C>T) is associated with cataract 12 multiple types (ClinVar).

How common is BFSP2 p.Arg5Ter (c.13C>T) in the general population?

BFSP2 p.Arg5Ter (c.13C>T) is very rare (popmax 0.00271%, nfe) (gnomAD).

BFSP2 p.Arg5Ter

c.13C>T · rs1224719314 · VCV1031336

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Conditions

cataract 12 multiple types

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 1 of 7
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.38	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.36	GERP -3, phastCons 0.048
Overall
CADD	34.0	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 0.00271% European (non-Finnish) · 32/1,180,030 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00204% 33/1,614,030 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,876
African / African-American	0.00133%	74,922

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: BFSP2
Protein: p.Arg5Ter
Coding: c.13C>T
MANE Select: NM_003571
dbSNP: rs1224719314
Type: single nucleotide variant
Location: chr3:133400096 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15
Residue 5: the 'disordered' region; the 'head' region

Full BFSP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 12 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BFSP2 p.Arg5Gln Uncertain significance ★ ⚠ same residue
BFSP2 p.Arg4Lys Uncertain significance ★★ ⚠ same condition
BFSP2 p.Arg72His Uncertain significance ★★ ⚠ same condition
BFSP2 p.Glu141Ala Uncertain significance ★★ ⚠ same condition
BFSP2 p.Glu289Asp Uncertain significance ★★ ⚠ same condition
BFSP2 p.Leu153Gln Uncertain significance ★★ ⚠ same condition
BFSP2 c.572+160A>G Benign ★★ same condition
BFSP2 c.730-7T>C Benign/Likely benign ★★ 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/bfsp2-p-arg5ter (accessed [today's date]).

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