Is BFSP1 p.Arg565Trp (c.1693C>T) pathogenic?

BFSP1 p.Arg565Trp (c.1693C>T) is classified Uncertain significance in BFSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). AlphaMissense: likely benign (0.1028); Ultra-rare (popmax 0.0254%, afr); Associated with Inborn genetic diseases.

What condition is associated with BFSP1 p.Arg565Trp (c.1693C>T)?

BFSP1 p.Arg565Trp (c.1693C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BFSP1 p.Arg565Trp (c.1693C>T) in the general population?

BFSP1 p.Arg565Trp (c.1693C>T) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

What do computational predictors say about BFSP1 p.Arg565Trp (c.1693C>T)?

AlphaMissense predicts likely benign (score 0.1028) — an in-silico prediction, not a clinical call.

BFSP1 p.Arg565Trp

c.1693C>T · rs148281730 · VCV3133778

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1028 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1028	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -9.22	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 0.39	GERP -1.4, phastCons 0.57
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	19.87	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 0.0254% African / African-American · 19/74,908 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00874% 141/1,614,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,943
European (non-Finnish)	0.00992%	10,086
East Asian	0.00445%	22,449
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Admixed American	0.00167%	60,002
South Asian	0.0011%	91,072

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.Arg565Trp
Coding: c.1693C>T
MANE Select: NM_001195
dbSNP: rs148281730
Type: single nucleotide variant
Location: chr20:17494379 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 565: the 'tail' region; the 'disordered' 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

Similar variants

BFSP1 p.Arg565Gln Likely benign ★ same residue
BFSP1 p.Asp19Asn Uncertain significance ★★ ⚠ same condition
BFSP1 p.Gln294Arg Uncertain significance ★★ ⚠ same condition
BFSP1 p.Glu93Asp Uncertain significance ★★ ⚠ same condition
BFSP1 p.Ile631Asn Uncertain significance ★★ ⚠ same condition
BFSP1 p.Leu68Phe Uncertain significance ★★ ⚠ same condition
BFSP1 p.Ser94Arg Uncertain significance ★★ ⚠ same condition
BFSP1 p.Thr490Ala 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-arg565trp (accessed [today's date]).

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