Is BFSP1 p.Ala219= (c.657C>T) pathogenic?

BFSP1 p.Ala219= (c.657C>T) is classified Benign in BFSP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-07-31). Rare (popmax 0.276%, sas); Associated with cataract 33.

What condition is associated with BFSP1 p.Ala219= (c.657C>T)?

BFSP1 p.Ala219= (c.657C>T) is associated with cataract 33 (ClinVar).

How common is BFSP1 p.Ala219= (c.657C>T) in the general population?

BFSP1 p.Ala219= (c.657C>T) is rare (popmax 0.276%, sas) (gnomAD).

BFSP1 p.Ala219=

c.657C>T · rs150736032 · VCV3032569

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.276%, sas)

Conditions

cataract 33

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 -6.4	GERP -5.6
Overall
CADD	0.505	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.276% South Asian · 243/88,118 alleles

Filtering AF 0.247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.236%

Overall 0.0185% 296/1,600,568 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.276%	363
Remaining individualsnot grpmax-eligible	0.0178%	5,632
Admixed American	0.00343%	29,150
European (non-Finnish)	0.00332%	30,116
African / African-American	0.00134%	74,638

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.Ala219=
Coding: c.657C>T
MANE Select: NM_001195
dbSNP: rs150736032
Type: single nucleotide variant
Location: chr20:17508967 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 219: 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.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
BFSP1 p.Leu68Phe 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-ala219 (accessed [today's date]).

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