Is BFAR p.Arg245His (c.734G>A) pathogenic?

BFAR p.Arg245His (c.734G>A) is classified Benign in BFAR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-30). AlphaMissense: likely benign (0.0913); Low-frequency (popmax 3.42%, afr).

How common is BFAR p.Arg245His (c.734G>A) in the general population?

BFAR p.Arg245His (c.734G>A) is low-frequency (popmax 3.42%, afr) (gnomAD).

What do computational predictors say about BFAR p.Arg245His (c.734G>A)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

BFAR p.Arg245His

c.734G>A · rs35377618 · VCV776979

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.42%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -8.93	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 6.7	phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 23 kb · p 0.11 · regional, not allelic
Overall
CADD	27.8	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 3.42% African / African-American · 2,538/74,292 alleles

Filtering AF 3.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.26%

Overall 0.185% 2,959/1,601,272 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.42%	29
Remaining individualsnot grpmax-eligible	0.235%	426
Middle Eastern	0.2%	501
Admixed American	0.193%	518
European (non-Finnish)	0.0116%	8,636
East Asian	0.0113%	8,864
South Asian	0.0112%	8,895
Finnishnot grpmax-eligible	0.00158%	63,112

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.Arg245His
Coding: c.734G>A
MANE Select: NM_016561
dbSNP: rs35377618
Type: single nucleotide variant
Location: chr16:14655161 (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.Arg245Cys Uncertain significance ★ ⚠ 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-arg245his (accessed [today's date]).

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