Is BFSP1 p.Cys131Ter (c.393C>A) pathogenic?

BFSP1 p.Cys131Ter (c.393C>A) is classified Uncertain significance in BFSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-30). Very rare (popmax 0.0011%, sas).

How common is BFSP1 p.Cys131Ter (c.393C>A) in the general population?

BFSP1 p.Cys131Ter (c.393C>A) is very rare (popmax 0.0011%, sas) (gnomAD).

BFSP1 p.Cys131Ter

c.393C>A · VCV3362055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, 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 2 of 8
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -3.5, phastCons 0.11
Overall
CADD	35.0	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 0.0011% South Asian · 1/91,072 alleles

Overall 6.84e-05% 1/1,461,776 alleles · very rare

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: BFSP1
Protein: p.Cys131Ter
Coding: c.393C>A
MANE Select: NM_001195
Type: single nucleotide variant
Location: chr20:17524893 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 131: the if rod domain; the 'coil 1b' region

Full BFSP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BFSP1 p.Ala643Thr Uncertain significance ★★ ⚠ same type
BFSP1 p.Arg560Cys Uncertain significance ★★ ⚠ same type
BFSP1 p.Arg69Trp Uncertain significance ★★ ⚠ same type
BFSP1 p.Asp19Asn Uncertain significance ★★ ⚠ same type
BFSP1 p.Gln294Arg Uncertain significance ★★ ⚠ same type
BFSP1 p.Glu93Asp Uncertain significance ★★ ⚠ same type
BFSP1 p.Gly46Trp Uncertain significance ★★ ⚠ same type
BFSP1 p.Ile271Thr 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/bfsp1-p-cys131ter (accessed [today's date]).

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