Is BFSP1 p.Asp19Asn (c.55G>A) pathogenic?

BFSP1 p.Asp19Asn (c.55G>A) is classified Uncertain significance in BFSP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-26). AlphaMissense: likely benign (0.1152); Very rare (popmax 0.00262%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BFSP1 p.Asp19Asn (c.55G>A)?

BFSP1 p.Asp19Asn (c.55G>A) is associated with Inborn genetic diseases, cataract 33 (ClinVar).

How common is BFSP1 p.Asp19Asn (c.55G>A) in the general population?

BFSP1 p.Asp19Asn (c.55G>A) is very rare (popmax 0.00262%, nfe) (gnomAD).

What do computational predictors say about BFSP1 p.Asp19Asn (c.55G>A)?

AlphaMissense predicts likely benign (score 0.1152) — an in-silico prediction, not a clinical call.

BFSP1 p.Asp19Asn

c.55G>A · rs1490233749 · VCV2721088

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1152 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00262%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1152	likely benign
REVEL	0.315	indeterminate
SaProt	LLR -8.25	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.16, phastCons 0.23
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00262% European (non-Finnish) · 29/1,108,154 alleles

Filtering AF 0.00184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00159%

Overall 0.00199% 29/1,458,980 alleles · very rare

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.Asp19Asn
Coding: c.55G>A
MANE Select: NM_001195
dbSNP: rs1490233749
Type: single nucleotide variant
Location: chr20:17531275 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 19: the 'head' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cataract 33

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.Gln294Arg Uncertain significance ★★ ⚠ same condition
BFSP1 p.Glu93Asp Uncertain significance ★★ ⚠ same condition
BFSP1 p.Gly46Trp Uncertain significance ★★ ⚠ same condition
BFSP1 p.Ile271Thr Uncertain significance ★★ ⚠ same condition
BFSP1 p.Ile631Asn 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-asp19asn (accessed [today's date]).

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