Is SBF1 p.Arg18Pro (c.53G>C) pathogenic?

SBF1 p.Arg18Pro (c.53G>C) is classified Uncertain significance in SBF1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-02-15). AlphaMissense: likely benign (0.2266); Very rare (popmax 0.00576%, nfe).

How common is SBF1 p.Arg18Pro (c.53G>C) in the general population?

SBF1 p.Arg18Pro (c.53G>C) is very rare (popmax 0.00576%, nfe) (gnomAD).

What do computational predictors say about SBF1 p.Arg18Pro (c.53G>C)?

AlphaMissense predicts likely benign (score 0.2266) — an in-silico prediction, not a clinical call.

SBF1 p.Arg18Pro

c.53G>C · rs1003479968 · VCV1162899

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2266 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00576%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2266	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -6.82	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	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 8,372 bp · p 0.4 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00576% European (non-Finnish) · 64/1,111,602 alleles

Filtering AF 0.00461% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0042%

Overall 0.00465% 68/1,462,354 alleles · very rare exomes 49/1,311,414 · genomes 19/150,940 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00576%	17,369
Remaining individualsnot grpmax-eligible	0.00358%	27,933
African / African-American	0.00296%	33,780

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.Arg18Pro
Coding: c.53G>C
MANE Select: NM_002972
dbSNP: rs1003479968
Type: single nucleotide variant
Location: chr22:50474788 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 18: the udenn domain

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

Similar variants

SBF1 p.Arg18Gly 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
SBF1 c.2643+6C>T Uncertain significance ★★ same type
SBF1 c.279+3C>T 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-arg18pro (accessed [today's date]).

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