Is SOBP p.Pro139Ser (c.415C>T) pathogenic?

SOBP p.Pro139Ser (c.415C>T) is classified Uncertain significance in SOBP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-11). AlphaMissense: likely benign (0.3289); Ultra-rare (popmax 0.0633%, amr); Associated with intellectual disability, anterior maxillary protrusion, and strabismus.

What condition is associated with SOBP p.Pro139Ser (c.415C>T)?

SOBP p.Pro139Ser (c.415C>T) is associated with intellectual disability, anterior maxillary protrusion, and strabismus (ClinVar).

How common is SOBP p.Pro139Ser (c.415C>T) in the general population?

SOBP p.Pro139Ser (c.415C>T) is ultra-rare (popmax 0.0633%, amr) (gnomAD).

What do computational predictors say about SOBP p.Pro139Ser (c.415C>T)?

AlphaMissense predicts likely benign (score 0.3289) — an in-silico prediction, not a clinical call.

SOBP p.Pro139Ser

c.415C>T · rs761098848 · VCV1032014

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3289 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0633%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, anterior maxillary protrusion, and strabismus

Computational evidence

Protein change
AlphaMissense	0.3289	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -6.65	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 5.9	GERP 5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 30 kb · p 0.59 · regional, not allelic
Overall
CADD	20.9	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 0.0633% Admixed American · 38/60,002 alleles

Filtering AF 0.0474% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0418%

Overall 0.00254% 41/1,613,920 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0633%	1,579
Remaining individualsnot grpmax-eligible	0.0032%	31,237
African / African-American	0.00133%	74,914

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.Pro139Ser
Coding: c.415C>T
MANE Select: NM_018013
dbSNP: rs761098848
Type: single nucleotide variant
Location: chr6:107506421 (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

Disease context

intellectual disability, anterior maxillary protrusion, and strabismus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SOBP p.Pro139Gln Uncertain significance ★ ⚠ same residue
SOBP p.Ala208Thr Uncertain significance ★★ ⚠ same condition
SOBP p.Pro441Ser Uncertain significance ★★ ⚠ same condition
SOBP p.Pro577Ser Uncertain significance ★★ ⚠ same condition
SOBP p.Pro472= Benign/Likely benign ★★ same condition
SOBP p.Ser683Gly Benign ★★ same condition
SOBP c.574-3C>T Uncertain significance ★ same condition
SOBP p.Asn721Lys Uncertain significance ★ ⚠ same condition

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-pro139ser (accessed [today's date]).

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