Is SBF1 p.Arg97= (c.291C>T) pathogenic?

SBF1 p.Arg97= (c.291C>T) is classified Benign in SBF1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Common (popmax 24.8%, afr) — too common for a highly-penetrant pathogenic allele.

SBF1 p.Arg97=

Q: How common is SBF1 p.Arg97= (c.291C>T) in the general population?

SBF1 p.Arg97= (c.291C>T) is common (popmax 24.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.291C>T · rs6010103 · VCV1260956

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 24.8%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.36	GERP -2.8
Overall
CADD	2.257	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 24.8% African / African-American · 18,505/74,570 alleles

Filtering AF 24.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 24.4%

Overall 1.34% 21,548/1,612,612 alleles · common exomes 11,097/1,461,078 · genomes 10,451/151,534 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	24.8%	4
Remaining individualsnot grpmax-eligible	1.76%	57
Admixed American	1.45%	69
Middle Eastern	0.929%	108
Ashkenazi Jewishnot grpmax-eligible	0.457%	219
East Asian	0.352%	284
South Asian	0.175%	572
European (non-Finnish)	0.0474%	2,110
Finnishnot grpmax-eligible	0.0047%	21,263

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: SBF1
Protein: p.Arg97=
Coding: c.291C>T
MANE Select: NM_002972
dbSNP: rs6010103
Type: single nucleotide variant
Location: chr22:50467679 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 97: the udenn domain; the 'disordered' region

Full SBF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SBF1 p.Arg97Cys Uncertain significance ★ ⚠ same residue
SBF1 p.Arg97His Uncertain significance ★ ⚠ same residue
SBF1 p.Arg97Leu Uncertain significance ★ ⚠ same residue
SBF1 c.3826+1G>A Pathogenic/Likely pathogenic ★★ same type
SBF1 p.Met417Val Pathogenic/Likely pathogenic ★★ ⚠ same type
SBF1 c.1431+6A>T Uncertain significance ★★ same type
SBF1 c.1636+4C>T Uncertain significance ★★ same type
SBF1 c.1899+3G>A 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/sbf1-p-arg97 (accessed [today's date]).

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