Is BFSP2 p.Arg339Cys (c.1015C>T) pathogenic?

BFSP2 p.Arg339Cys (c.1015C>T) is classified Uncertain significance in BFSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-26). AlphaMissense: likely benign (0.1428); Very rare (popmax 0.00333%, amr).

How common is BFSP2 p.Arg339Cys (c.1015C>T) in the general population?

BFSP2 p.Arg339Cys (c.1015C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about BFSP2 p.Arg339Cys (c.1015C>T)?

AlphaMissense predicts likely benign (score 0.1428) — an in-silico prediction, not a clinical call.

BFSP2 p.Arg339Cys

c.1015C>T · rs200573601 · VCV2227638

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1428 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1428	likely benign
REVEL	0.71	pathogenic-leaning
SaProt	LLR -8.05	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP 0.96, phastCons 0.002
Regional constraint	o/e 0.99	unconstrained · MANE · 75 kb · p 0.73 · regional, not allelic
Overall
CADD	24.2	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 0.00333% Admixed American · 2/59,994 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00173% 28/1,613,934 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,997
East Asian	0.00223%	44,884
European (non-Finnish)	0.00195%	51,303
Remaining individualsnot grpmax-eligible	0.0016%	62,480
South Asian	0.0011%	91,088

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.Arg339Cys
Coding: c.1015C>T
MANE Select: NM_003571
dbSNP: rs200573601
Type: single nucleotide variant
Location: chr3:133466951 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15
Residue 339: the if rod domain

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

Similar variants

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
BFSP2 p.Gly79Ser 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-arg339cys (accessed [today's date]).

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