Is SOBP p.Pro348Ala (c.1042C>G) pathogenic?

SOBP p.Pro348Ala (c.1042C>G) is classified Uncertain significance in SOBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-26). AlphaMissense: likely benign (0.075); Very rare (popmax 0.00212%, nfe).

How common is SOBP p.Pro348Ala (c.1042C>G) in the general population?

SOBP p.Pro348Ala (c.1042C>G) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about SOBP p.Pro348Ala (c.1042C>G)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

SOBP p.Pro348Ala

c.1042C>G · VCV3959581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.075	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -7.56	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 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 564 bp · p 0.0029 · regional, not allelic
Overall
CADD	25.1	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 0.00212% European (non-Finnish) · 25/1,180,044 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00155% 25/1,614,096 alleles · very rare exomes 22/1,461,876 · genomes 3/152,220 · 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.Pro348Ala
Coding: c.1042C>G
MANE Select: NM_018013
Type: single nucleotide variant
Location: chr6:107633886 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 52.41

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-pro348ala (accessed [today's date]).

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