Is BFSP1 p.Thr648Ala (c.1942A>G) pathogenic?

BFSP1 p.Thr648Ala (c.1942A>G) is classified Uncertain significance in BFSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-13). AlphaMissense: ambiguous (0.3785); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with BFSP1 p.Thr648Ala (c.1942A>G)?

BFSP1 p.Thr648Ala (c.1942A>G) is associated with Inborn genetic diseases (ClinVar).

How common is BFSP1 p.Thr648Ala (c.1942A>G) in the general population?

BFSP1 p.Thr648Ala (c.1942A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about BFSP1 p.Thr648Ala (c.1942A>G)?

AlphaMissense predicts ambiguous (score 0.3785) — an in-silico prediction, not a clinical call.

BFSP1 p.Thr648Ala

c.1942A>G · VCV3824225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3785 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3785	ambiguous
REVEL	0.488	indeterminate
SaProt	LLR -7.75	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	24.1	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 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000137% 2/1,461,806 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	8.47e-05%	1,180,022

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.Thr648Ala
Coding: c.1942A>G
MANE Select: NM_001195
Type: single nucleotide variant
Location: chr20:17494130 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 648: the 'tail' 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.Thr648Ile 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-thr648ala (accessed [today's date]).

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