Is BFAR p.Arg245Cys (c.733C>T) pathogenic?

BFAR p.Arg245Cys (c.733C>T) is classified Uncertain significance in BFAR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.1648); Ultra-rare (popmax 0.0158%, eas).

How common is BFAR p.Arg245Cys (c.733C>T) in the general population?

BFAR p.Arg245Cys (c.733C>T) is ultra-rare (popmax 0.0158%, eas) (gnomAD).

What do computational predictors say about BFAR p.Arg245Cys (c.733C>T)?

AlphaMissense predicts likely benign (score 0.1648) — an in-silico prediction, not a clinical call.

BFAR p.Arg245Cys

c.733C>T · rs768962951 · VCV2264955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1648 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0158%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1648	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -11.27	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 23 kb · p 0.11 · regional, not allelic
Overall
CADD	23.7	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 0.0158% East Asian · 7/44,426 alleles

Filtering AF 0.00732% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00519%

Overall 0.00186% 27/1,452,182 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0158%	6,347
South Asian	0.00448%	22,339
Remaining individualsnot grpmax-eligible	0.00162%	61,894
European (non-Finnish)	0.00128%	78,364

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: BFAR
Protein: p.Arg245Cys
Coding: c.733C>T
MANE Select: NM_016561
dbSNP: rs768962951
Type: single nucleotide variant
Location: chr16:14655160 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.40
Residue 245: the sam domain; a UniProt-annotated variant site (in)

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

Similar variants

BFAR p.Arg245His Benign ★★ ⚠ same residue
BFAR p.Ala156Val Uncertain significance ★ ⚠ same type
BFAR p.Ala238Thr Uncertain significance ★ ⚠ same type
BFAR p.Ala238Val Uncertain significance ★ ⚠ same type
BFAR p.Ala59Val Uncertain significance ★ ⚠ same type
BFAR p.Ala90Val Uncertain significance ★ ⚠ same type
BFAR p.Ala98Thr Uncertain significance ★ ⚠ same type
BFAR p.Arg135Pro 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/bfar-p-arg245cys (accessed [today's date]).

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