Is BFSP2 p.Gly55Arg (c.163G>A) pathogenic?

BFSP2 p.Gly55Arg (c.163G>A) is classified Conflicting classifications of pathogenicity in BFSP2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-10-03). AlphaMissense: likely benign (0.1058); Ultra-rare (popmax 0.0318%, sas); Associated with cataract 12 multiple types.

What condition is associated with BFSP2 p.Gly55Arg (c.163G>A)?

BFSP2 p.Gly55Arg (c.163G>A) is associated with cataract 12 multiple types (ClinVar).

How common is BFSP2 p.Gly55Arg (c.163G>A) in the general population?

BFSP2 p.Gly55Arg (c.163G>A) is ultra-rare (popmax 0.0318%, sas) (gnomAD).

What do computational predictors say about BFSP2 p.Gly55Arg (c.163G>A)?

AlphaMissense predicts likely benign (score 0.1058) — an in-silico prediction, not a clinical call.

BFSP2 p.Gly55Arg

c.163G>A · rs756829125 · VCV2315690

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1058 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0318%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 12 multiple types

Computational evidence

Protein change
AlphaMissense	0.1058	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -5.98	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 4.2	GERP -0.55, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 75 kb · p 0.73 · regional, not allelic
Overall
CADD	15.29	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 0.0318% South Asian · 29/91,076 alleles

Filtering AF 0.0228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0196%

Overall 0.00273% 44/1,613,786 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0318%	3,141
African / African-American	0.0107%	9,365
Remaining individualsnot grpmax-eligible	0.0032%	31,237
European (non-Finnish)	0.000424%	235,984

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.Gly55Arg
Coding: c.163G>A
MANE Select: NM_003571
dbSNP: rs756829125
Type: single nucleotide variant
Location: chr3:133400246 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15
Residue 55: 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.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-gly55arg (accessed [today's date]).

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