Is BFSP1 p.Ser94Arg (c.280A>C) pathogenic?

BFSP1 p.Ser94Arg (c.280A>C) is classified Uncertain significance in BFSP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-18). AlphaMissense: likely benign (0.297); Ultra-rare (popmax 0.0291%, amr); Associated with Inborn genetic diseases.

What condition is associated with BFSP1 p.Ser94Arg (c.280A>C)?

BFSP1 p.Ser94Arg (c.280A>C) is associated with Inborn genetic diseases, cataract 33 (ClinVar).

How common is BFSP1 p.Ser94Arg (c.280A>C) in the general population?

BFSP1 p.Ser94Arg (c.280A>C) is ultra-rare (popmax 0.0291%, amr) (gnomAD).

What do computational predictors say about BFSP1 p.Ser94Arg (c.280A>C)?

AlphaMissense predicts likely benign (score 0.297) — an in-silico prediction, not a clinical call.

BFSP1 p.Ser94Arg

c.280A>C · rs913200482 · VCV2393314

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.297 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0291%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.297	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -5.18	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 0.029	GERP -1.7, phastCons 0.7
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	19.44	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0291% Admixed American · 10/34,350 alleles

Filtering AF 0.0157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.012%

Overall 0.000988% 14/1,416,840 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0291%	3,435
Remaining individualsnot grpmax-eligible	0.00555%	18,012
African / African-American	0.0015%	66,812

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.Ser94Arg
Coding: c.280A>C
MANE Select: NM_001195
dbSNP: rs913200482
Type: single nucleotide variant
Location: chr20:17531050 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 94: the if rod domain; the 'coil 1b' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cataract 33

Similar variants

BFSP1 p.Ala643Thr Uncertain significance ★★ ⚠ same condition
BFSP1 p.Arg560Cys Uncertain significance ★★ ⚠ same condition
BFSP1 p.Arg69Trp Uncertain significance ★★ same condition
BFSP1 p.Asp19Asn Uncertain significance ★★ ⚠ same condition
BFSP1 p.Gln294Arg Uncertain significance ★★ ⚠ same condition
BFSP1 p.Glu93Asp Uncertain significance ★★ ⚠ same condition
BFSP1 p.Gly46Trp Uncertain significance ★★ ⚠ same condition
BFSP1 p.Ile271Thr 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/bfsp1-p-ser94arg (accessed [today's date]).

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