Is BFSP2 p.Asp9Glu (c.27C>G) pathogenic?

BFSP2 p.Asp9Glu (c.27C>G) is classified Uncertain significance in BFSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-03). AlphaMissense: likely benign (0.1047); Very rare (popmax 8.47e-05%, nfe); Associated with cataract 12 multiple types.

What condition is associated with BFSP2 p.Asp9Glu (c.27C>G)?

BFSP2 p.Asp9Glu (c.27C>G) is associated with cataract 12 multiple types (ClinVar).

How common is BFSP2 p.Asp9Glu (c.27C>G) in the general population?

BFSP2 p.Asp9Glu (c.27C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about BFSP2 p.Asp9Glu (c.27C>G)?

AlphaMissense predicts likely benign (score 0.1047) — an in-silico prediction, not a clinical call.

BFSP2 p.Asp9Glu

c.27C>G · rs2073348739 · VCV2439510

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1047 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 12 multiple types

Computational evidence

Protein change
AlphaMissense	0.1047	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -5.47	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 -6.6	GERP -2.3
Regional constraint	o/e 0.99	unconstrained · MANE · 75 kb · p 0.73 · regional, not allelic
Overall
CADD	1.166	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 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.84e-05% 1/1,461,840 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: BFSP2
Protein: p.Asp9Glu
Coding: c.27C>G
MANE Select: NM_003571
dbSNP: rs2073348739
Type: single nucleotide variant
Location: chr3:133400110 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15
Residue 9: the 'disordered' region; the 'head' region

Full BFSP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 12 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BFSP2 p.Arg4Lys Uncertain significance ★★ ⚠ same condition
BFSP2 p.Arg5Ter Uncertain significance ★★ same condition
BFSP2 p.Arg72His Uncertain significance ★★ ⚠ same condition
BFSP2 p.Glu141Ala Uncertain significance ★★ ⚠ same condition
BFSP2 p.Glu289Asp Uncertain significance ★★ ⚠ same condition
BFSP2 p.Leu153Gln Uncertain significance ★★ ⚠ same condition
BFSP2 c.572+160A>G Benign ★★ same condition
BFSP2 c.730-7T>C Benign/Likely benign ★★ 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/bfsp2-p-asp9glu (accessed [today's date]).

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