Is BFSP2 p.Ala379Glu (c.1136C>A) pathogenic?

BFSP2 p.Ala379Glu (c.1136C>A) is classified Benign in BFSP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-07-29). AlphaMissense: likely benign (0.1093); Very rare (popmax 0.00212%, nfe); Associated with Developmental cataract.

What condition is associated with BFSP2 p.Ala379Glu (c.1136C>A)?

BFSP2 p.Ala379Glu (c.1136C>A) is associated with Developmental cataract (ClinVar).

How common is BFSP2 p.Ala379Glu (c.1136C>A) in the general population?

BFSP2 p.Ala379Glu (c.1136C>A) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about BFSP2 p.Ala379Glu (c.1136C>A)?

AlphaMissense predicts likely benign (score 0.1093) — an in-silico prediction, not a clinical call.

BFSP2 p.Ala379Glu

c.1136C>A · rs774824478 · VCV252953

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1093 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Developmental cataract

Computational evidence

Protein change
AlphaMissense	0.1093	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -7.11	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 0.36	GERP -0.38
Regional constraint	o/e 0.99	unconstrained · MANE · 75 kb · p 0.73 · regional, not allelic
Overall
CADD	10.48	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 0.00212% European (non-Finnish) · 25/1,180,028 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00167% 27/1,613,876 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,201
African / African-American	0.00133%	74,936
South Asian	0.0011%	91,074

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.Ala379Glu
Coding: c.1136C>A
MANE Select: NM_003571
dbSNP: rs774824478
Type: single nucleotide variant
Location: chr3:133472457 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15
Residue 379: a UniProt-annotated variant site (in ctrct12; uncertain significance); the if rod domain

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

Disease context

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

Similar variants

BFSP2 p.Arg89Trp Uncertain significance ⚠ same condition
BFSP2 p.Arg4Lys Uncertain significance ★★ ⚠ same type
BFSP2 p.Arg52Gln Uncertain significance ★★ ⚠ same type
BFSP2 p.Arg5Ter Uncertain significance ★★ same type
BFSP2 p.Arg72His Uncertain significance ★★ ⚠ same type
BFSP2 p.Glu141Ala Uncertain significance ★★ ⚠ same type
BFSP2 p.Glu228Gly Uncertain significance ★★ ⚠ same type
BFSP2 p.Glu289Asp Uncertain significance ★★ ⚠ same type

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-ala379glu (accessed [today's date]).

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