Is SOBP p.Ser464Arg (c.1390A>C) pathogenic?

SOBP p.Ser464Arg (c.1390A>C) is classified Uncertain significance in SOBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). AlphaMissense: likely pathogenic (0.9375); Very rare (popmax 0.0058%, afr).

How common is SOBP p.Ser464Arg (c.1390A>C) in the general population?

SOBP p.Ser464Arg (c.1390A>C) is very rare (popmax 0.0058%, afr) (gnomAD).

What do computational predictors say about SOBP p.Ser464Arg (c.1390A>C)?

AlphaMissense predicts likely pathogenic (score 0.9375) — an in-silico prediction, not a clinical call.

SOBP p.Ser464Arg

c.1390A>C · VCV3799763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9375 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0058%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9375	likely pathogenic
REVEL	0.093	moderately benign-leaning
SaProt	LLR -6.74	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,273 bp · p 0.16 · regional, not allelic
Overall
CADD	23.3	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 0.0058% African / African-American · 4/68,984 alleles

Filtering AF 0.00195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00111%

Overall 0.000323% 5/1,547,654 alleles · very rare exomes 2/1,408,714 · genomes 3/138,940 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0058%	17,246
European (non-Finnish)	8.71e-05%	1,148,104

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.Ser464Arg
Coding: c.1390A>C
MANE Select: NM_018013
Type: single nucleotide variant
Location: chr6:107634234 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 52.41
Residue 464: 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-ser464arg (accessed [today's date]).

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