Is BFSP1 p.Arg229Trp (c.685C>T) pathogenic?

BFSP1 p.Arg229Trp (c.685C>T) is classified Uncertain significance in BFSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-16). AlphaMissense: likely benign (0.1519); Ultra-rare (popmax 0.0165%, mid); Associated with cataract 33.

What condition is associated with BFSP1 p.Arg229Trp (c.685C>T)?

BFSP1 p.Arg229Trp (c.685C>T) is associated with cataract 33 (ClinVar).

How common is BFSP1 p.Arg229Trp (c.685C>T) in the general population?

BFSP1 p.Arg229Trp (c.685C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about BFSP1 p.Arg229Trp (c.685C>T)?

AlphaMissense predicts likely benign (score 0.1519) — an in-silico prediction, not a clinical call.

BFSP1 p.Arg229Trp

c.685C>T · rs372210205 · VCV1009059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1519 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 33

Computational evidence

Protein change
AlphaMissense	0.1519	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -10.18	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -1.2, phastCons 0.8
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.00908% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00847%

Overall 0.00866% 139/1,605,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
European (non-Finnish)	0.0106%	9,412
Remaining individualsnot grpmax-eligible	0.00966%	10,352
African / African-American	0.00536%	18,651
East Asian	0.00226%	44,296
South Asian	0.00224%	44,568

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.Arg229Trp
Coding: c.685C>T
MANE Select: NM_001195
dbSNP: rs372210205
Type: single nucleotide variant
Location: chr20:17508939 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 229: the if rod domain; the 'coil 2' region

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

Disease context

cataract 33 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BFSP1 p.Arg229Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
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.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-arg229trp (accessed [today's date]).

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