Is BFSP2 p.Ser82= (c.246T>C) pathogenic?

BFSP2 p.Ser82= (c.246T>C) is classified Benign in BFSP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-24). Rare (popmax 0.865%, sas); Associated with cataract 12 multiple types.

What condition is associated with BFSP2 p.Ser82= (c.246T>C)?

BFSP2 p.Ser82= (c.246T>C) is associated with cataract 12 multiple types (ClinVar).

How common is BFSP2 p.Ser82= (c.246T>C) in the general population?

BFSP2 p.Ser82= (c.246T>C) is rare (popmax 0.865%, sas) (gnomAD).

BFSP2 p.Ser82=

c.246T>C · rs145934653 · VCV343401

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.865%, sas)

Conditions

cataract 12 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -3.2
Overall
CADD	7.776	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.865% South Asian · 788/91,086 alleles

Filtering AF 0.815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.795%

Overall 0.12% 1,929/1,614,030 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.54%	65
South Asiangrpmax	0.865%	116
Middle Eastern	0.726%	138
Ashkenazi Jewishnot grpmax-eligible	0.189%	529
Remaining individualsnot grpmax-eligible	0.176%	568
European (non-Finnish)	0.0746%	1,341
Admixed American	0.03%	3,335
Finnishnot grpmax-eligible	0.0157%	6,386
African / African-American	0.012%	8,340

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser82=
Coding: c.246T>C
MANE Select: NM_003571
dbSNP: rs145934653
Type: single nucleotide variant
Location: chr3:133400329 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15
Residue 82: 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-ser82 (accessed [today's date]).

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