Is BFSP1 p.Arg69Gln (c.206G>A) pathogenic?

BFSP1 p.Arg69Gln (c.206G>A) is classified Uncertain significance in BFSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.1531); Very rare (popmax 0.00628%, eas); Associated with Inborn genetic diseases.

What condition is associated with BFSP1 p.Arg69Gln (c.206G>A)?

BFSP1 p.Arg69Gln (c.206G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BFSP1 p.Arg69Gln (c.206G>A) in the general population?

BFSP1 p.Arg69Gln (c.206G>A) is very rare (popmax 0.00628%, eas) (gnomAD).

What do computational predictors say about BFSP1 p.Arg69Gln (c.206G>A)?

AlphaMissense predicts likely benign (score 0.1531) — an in-silico prediction, not a clinical call.

BFSP1 p.Arg69Gln

c.206G>A · rs376904264 · VCV2557083

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1531 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00628%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1531	likely benign
REVEL	0.48	indeterminate
SaProt	LLR -6.00	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 4.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	26.5	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 0.00628% East Asian · 2/31,858 alleles

Filtering AF 0.00104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000389%

Overall 0.0003% 4/1,333,914 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00628%	15,929
Remaining individualsnot grpmax-eligible	0.004%	24,992

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.Arg69Gln
Coding: c.206G>A
MANE Select: NM_001195
dbSNP: rs376904264
Type: single nucleotide variant
Location: chr20:17531124 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 69: the if rod domain; the 'coil 1a' 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.Arg69Trp 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-arg69gln (accessed [today's date]).

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