Is BFSP1 p.Ala60Asp (c.179C>A) pathogenic?

BFSP1 p.Ala60Asp (c.179C>A) is classified Uncertain significance in BFSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: ambiguous (0.4501); Very rare (popmax 0.00772%, afr); Associated with Inborn genetic diseases.

What condition is associated with BFSP1 p.Ala60Asp (c.179C>A)?

BFSP1 p.Ala60Asp (c.179C>A) is associated with Inborn genetic diseases (ClinVar).

How common is BFSP1 p.Ala60Asp (c.179C>A) in the general population?

BFSP1 p.Ala60Asp (c.179C>A) is very rare (popmax 0.00772%, afr) (gnomAD).

What do computational predictors say about BFSP1 p.Ala60Asp (c.179C>A)?

AlphaMissense predicts ambiguous (score 0.4501) — an in-silico prediction, not a clinical call.

BFSP1 p.Ala60Asp

c.179C>A · VCV4206552

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4501 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00772%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4501	ambiguous
REVEL	0.55	indeterminate
SaProt	LLR -6.93	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.5, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	23.1	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 0.00772% African / African-American · 5/64,768 alleles

Filtering AF 0.00295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00194%

Overall 0.000383% 5/1,306,532 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.Ala60Asp
Coding: c.179C>A
MANE Select: NM_001195
Type: single nucleotide variant
Location: chr20:17531151 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 60: 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.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
BFSP1 p.Val480Leu 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-ala60asp (accessed [today's date]).

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