Is SOBP p.Pro415Arg (c.1244C>G) pathogenic?

SOBP p.Pro415Arg (c.1244C>G) is classified Uncertain significance in SOBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: ambiguous (0.4824); Very rare (popmax 8.52e-05%, nfe).

How common is SOBP p.Pro415Arg (c.1244C>G) in the general population?

SOBP p.Pro415Arg (c.1244C>G) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

What do computational predictors say about SOBP p.Pro415Arg (c.1244C>G)?

AlphaMissense predicts ambiguous (score 0.4824) — an in-silico prediction, not a clinical call.

SOBP p.Pro415Arg

c.1244C>G · VCV4829876

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4824 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4824	ambiguous
REVEL	0.306	indeterminate
SaProt	LLR -9.74	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.72, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 564 bp · p 0.0029 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.52e-05% European (non-Finnish) · 1/1,173,316 alleles

Overall 6.25e-05% 1/1,601,192 alleles · very rare exomes 1/1,448,924 · genomes 0/152,268 · joint denominator

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: SOBP
Protein: p.Pro415Arg
Coding: c.1244C>G
MANE Select: NM_018013
Type: single nucleotide variant
Location: chr6:107634088 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 52.41
Residue 415: the 'disordered' region

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

Similar variants

SOBP c.573+12G>A Uncertain significance ★★ same type
SOBP p.Ala208Thr Uncertain significance ★★ ⚠ same type
SOBP p.Ala702Val Uncertain significance ★★ ⚠ same type
SOBP p.Glu89Lys Uncertain significance ★★ ⚠ same type
SOBP p.Lys862Asn Uncertain significance ★★ ⚠ same type
SOBP p.Pro138Leu Uncertain significance ★★ same type
SOBP p.Pro139Ser Uncertain significance ★★ ⚠ same type
SOBP p.Pro441Ser 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/sobp-p-pro415arg (accessed [today's date]).

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