Is SOBP p.Pro682Ser (c.2044C>T) pathogenic?

SOBP p.Pro682Ser (c.2044C>T) is classified Uncertain significance in SOBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). AlphaMissense: likely benign (0.0827); Very rare (popmax 0.000585%, nfe).

How common is SOBP p.Pro682Ser (c.2044C>T) in the general population?

SOBP p.Pro682Ser (c.2044C>T) is very rare (popmax 0.000585%, nfe) (gnomAD).

What do computational predictors say about SOBP p.Pro682Ser (c.2044C>T)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

SOBP p.Pro682Ser

c.2044C>T · rs1412564407 · VCV3167383

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000585%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -6.70	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 1.7	GERP 0.97, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,273 bp · p 0.16 · regional, not allelic
Overall
CADD	18.85	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 0.000585% European (non-Finnish) · 6/1,026,310 alleles

Filtering AF 0.00021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000138%

Overall 0.000454% 6/1,321,584 alleles · very rare exomes 6/1,172,764 · genomes 0/148,820 · 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.Pro682Ser
Coding: c.2044C>T
MANE Select: NM_018013
dbSNP: rs1412564407
Type: single nucleotide variant
Location: chr6:107634888 (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-pro682ser (accessed [today's date]).

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