Is SBF1 p.Ala403Pro (c.1207G>C) pathogenic?

SBF1 p.Ala403Pro (c.1207G>C) is classified Uncertain significance in SBF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-30). AlphaMissense: likely pathogenic (0.858); Absent from gnomAD v4.1.

How common is SBF1 p.Ala403Pro (c.1207G>C) in the general population?

SBF1 p.Ala403Pro (c.1207G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SBF1 p.Ala403Pro (c.1207G>C)?

AlphaMissense predicts likely pathogenic (score 0.858) — an in-silico prediction, not a clinical call.

SBF1 p.Ala403Pro

c.1207G>C · rs2148598257 · VCV1357548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.858 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.858	likely pathogenic
REVEL	0.387	indeterminate
SaProt	LLR -8.81	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.82	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 7.5	GERP 2.2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 19 kb · p 0.67 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A404P vs ClinVar A403P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SBF1
Protein: p.Ala403Pro
Coding: c.1207G>C
MANE Select: NM_002972
dbSNP: rs2148598257
Type: single nucleotide variant
Location: chr22:50465126 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 404 UniProt numbering: the ddenn 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-ala403pro (accessed [today's date]).

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