Is SBF1 p.Pro118Ser (c.352C>T) pathogenic?

SBF1 p.Pro118Ser (c.352C>T) is classified Uncertain significance in SBF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-04). AlphaMissense: likely benign (0.0659); Very rare (popmax 0.00401%, afr).

How common is SBF1 p.Pro118Ser (c.352C>T) in the general population?

SBF1 p.Pro118Ser (c.352C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about SBF1 p.Pro118Ser (c.352C>T)?

AlphaMissense predicts likely benign (score 0.0659) — an in-silico prediction, not a clinical call.

SBF1 p.Pro118Ser

c.352C>T · rs376316390 · VCV2417235

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0659 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0659	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.86	GERP -1.4, phastCons 0.21
Regional constraint	o/e 0.95	unconstrained · MANE · 8,372 bp · p 0.4 · regional, not allelic
Overall
CADD	5.013	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P119S vs ClinVar P118S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,906 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00112% 18/1,613,934 alleles · very rare exomes 14/1,461,838 · genomes 4/152,096 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,969
South Asian	0.00329%	30,360
European (non-Finnish)	0.00102%	98,331

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.Pro118Ser
Coding: c.352C>T
MANE Select: NM_002972
dbSNP: rs376316390
Type: single nucleotide variant
Location: chr22:50467618 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 119 UniProt numbering: the udenn domain; the 'disordered' region

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

Similar variants

SBF1 p.Pro118Ala 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-pro118ser (accessed [today's date]).

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