Is BFSP1 p.Arg565Gln (c.1694G>A) pathogenic?

BFSP1 p.Arg565Gln (c.1694G>A) is classified Likely benign in BFSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). AlphaMissense: likely benign (0.0723); Ultra-rare (popmax 0.0657%, mid); Associated with Inborn genetic diseases.

What condition is associated with BFSP1 p.Arg565Gln (c.1694G>A)?

BFSP1 p.Arg565Gln (c.1694G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BFSP1 p.Arg565Gln (c.1694G>A) in the general population?

BFSP1 p.Arg565Gln (c.1694G>A) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

What do computational predictors say about BFSP1 p.Arg565Gln (c.1694G>A)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

BFSP1 p.Arg565Gln

c.1694G>A · rs777235074 · VCV2529822

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.22	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 1.1	GERP -0.59, phastCons 0.64
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	13.96	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 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00211% 34/1,614,064 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
East Asian	0.00891%	11,226
Remaining individualsnot grpmax-eligible	0.008%	12,498
Admixed American	0.00333%	30,001
African / African-American	0.00267%	37,456
South Asian	0.0022%	45,540
European (non-Finnish)	0.00127%	78,669

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.Arg565Gln
Coding: c.1694G>A
MANE Select: NM_001195
dbSNP: rs777235074
Type: single nucleotide variant
Location: chr20:17494378 (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.Arg565Trp Uncertain significance ★ ⚠ 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-arg565gln (accessed [today's date]).

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