Is SBF1 p.Pro17Ser (c.49C>T) pathogenic?

SBF1 p.Pro17Ser (c.49C>T) is classified Uncertain significance in SBF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-03-14). AlphaMissense: likely benign (0.0815); Ultra-rare (popmax 0.0808%, eas).

How common is SBF1 p.Pro17Ser (c.49C>T) in the general population?

SBF1 p.Pro17Ser (c.49C>T) is ultra-rare (popmax 0.0808%, eas) (gnomAD).

What do computational predictors say about SBF1 p.Pro17Ser (c.49C>T)?

AlphaMissense predicts likely benign (score 0.0815) — an in-silico prediction, not a clinical call.

SBF1 p.Pro17Ser

c.49C>T · rs1263806867 · VCV1923630

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0815 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0808%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0815	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -7.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.3	GERP 0.55, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 8,372 bp · p 0.4 · regional, not allelic
Overall
CADD	24.0	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 0.0808% East Asian · 26/32,186 alleles

Filtering AF 0.0566% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0485%

Overall 0.00465% 68/1,461,214 alleles · ultra-rare exomes 61/1,310,188 · genomes 7/151,026 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0808%	1,238
Remaining individualsnot grpmax-eligible	0.00537%	18,609
European (non-Finnish)	0.00333%	30,025
South Asian	0.00256%	39,135

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.Pro17Ser
Coding: c.49C>T
MANE Select: NM_002972
dbSNP: rs1263806867
Type: single nucleotide variant
Location: chr22:50474792 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 17: the udenn domain

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

Similar variants

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
SBF1 c.3904+6G>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-pro17ser (accessed [today's date]).

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