Is BFSP2 p.Arg173Trp (c.517C>T) pathogenic?

BFSP2 p.Arg173Trp (c.517C>T) is classified Conflicting classifications of pathogenicity in BFSP2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-20). AlphaMissense: likely benign (0.1476); Ultra-rare (popmax 0.0166%, mid); Associated with cataract 12 multiple types.

What condition is associated with BFSP2 p.Arg173Trp (c.517C>T)?

BFSP2 p.Arg173Trp (c.517C>T) is associated with cataract 12 multiple types (ClinVar).

How common is BFSP2 p.Arg173Trp (c.517C>T) in the general population?

BFSP2 p.Arg173Trp (c.517C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about BFSP2 p.Arg173Trp (c.517C>T)?

AlphaMissense predicts likely benign (score 0.1476) — an in-silico prediction, not a clinical call.

BFSP2 p.Arg173Trp

c.517C>T · rs375380005 · VCV902120

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1476 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 12 multiple types

Computational evidence

Protein change
AlphaMissense	0.1476	likely benign
REVEL	0.737	pathogenic-leaning
SaProt	LLR -7.58	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.35	acceptor loss, 27 bp away · masked 0 · deltas
Pangolin	Δ0.20	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.97	GERP -1.8, phastCons 0.42
Regional constraint	o/e 0.99	unconstrained · MANE · 75 kb · p 0.73 · regional, not allelic
Overall
CADD	25.2	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 0.0166% Middle Eastern · 1/6,042 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00341% 55/1,613,816 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,042
Admixed American	0.0117%	8,569
Remaining individualsnot grpmax-eligible	0.0096%	10,413
Finnishnot grpmax-eligible	0.00312%	32,002
European (non-Finnish)	0.00297%	33,714
East Asian	0.00223%	44,884
South Asian	0.0022%	45,529
African / African-American	0.00134%	74,850

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.Arg173Trp
Coding: c.517C>T
MANE Select: NM_003571
dbSNP: rs375380005
Type: single nucleotide variant
Location: chr3:133447344 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15
Residue 173: the if rod domain

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.Arg4Lys Uncertain significance ★★ ⚠ same condition
BFSP2 p.Arg5Ter 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-arg173trp (accessed [today's date]).

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