Is SOBP p.Pro441Ser (c.1321C>T) pathogenic?

SOBP p.Pro441Ser (c.1321C>T) is classified Uncertain significance in SOBP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-10-31). AlphaMissense: likely benign (0.0872); Rare (popmax 0.318%, nfe); Associated with intellectual disability, anterior maxillary protrusion, and strabismus.

What condition is associated with SOBP p.Pro441Ser (c.1321C>T)?

SOBP p.Pro441Ser (c.1321C>T) is associated with intellectual disability, anterior maxillary protrusion, and strabismus (ClinVar).

How common is SOBP p.Pro441Ser (c.1321C>T) in the general population?

SOBP p.Pro441Ser (c.1321C>T) is rare (popmax 0.318%, nfe) (gnomAD).

What do computational predictors say about SOBP p.Pro441Ser (c.1321C>T)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

SOBP p.Pro441Ser

c.1321C>T · rs201319446 · VCV212276

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.318%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, anterior maxillary protrusion, and strabismus

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -7.95	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 7.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 564 bp · p 0.0029 · regional, not allelic
Overall
CADD	25.6	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 0.318% European (non-Finnish) · 3,750/1,179,486 alleles

Filtering AF 0.309% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.306%

Overall 0.25% 4,036/1,611,196 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.318%	315
Remaining individualsnot grpmax-eligible	0.24%	416
Admixed American	0.085%	1,176
African / African-American	0.0706%	1,416
Finnishnot grpmax-eligible	0.0501%	1,996
South Asian	0.0011%	91,016

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.Pro441Ser
Coding: c.1321C>T
MANE Select: NM_018013
dbSNP: rs201319446
Type: single nucleotide variant
Location: chr6:107634165 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 52.41
Residue 441: the 'disordered' region

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.Ala208Thr Uncertain significance ★★ ⚠ same condition
SOBP p.Pro139Ser 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
SOBP p.Gln604Lys Conflicting classifications of pathogenicity ★ ⚠ 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-pro441ser (accessed [today's date]).

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