Is SOBP p.His461Pro (c.1382A>C) pathogenic?

SOBP p.His461Pro (c.1382A>C) is classified Likely benign in SOBP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2013-08-07). AlphaMissense: likely benign (0.1954); Ultra-rare (popmax 0.0278%, afr).

How common is SOBP p.His461Pro (c.1382A>C) in the general population?

SOBP p.His461Pro (c.1382A>C) is ultra-rare (popmax 0.0278%, afr) (gnomAD).

What do computational predictors say about SOBP p.His461Pro (c.1382A>C)?

AlphaMissense predicts likely benign (score 0.1954) — an in-silico prediction, not a clinical call.

SOBP p.His461Pro

c.1382A>C · rs587780464 · VCV130357

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1954 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0278%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1954	likely benign
REVEL	0.328	indeterminate
SaProt	LLR -3.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,273 bp · p 0.16 · regional, not allelic
Overall
CADD	25.5	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 0.0278% African / African-American · 18/64,654 alleles

Filtering AF 0.0179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0148%

Overall 0.0071% 110/1,548,398 alleles · ultra-rare exomes 59/1,425,152 · genomes 51/123,246 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.139%	718
African / African-Americangrpmax	0.0278%	3,592
Finnishnot grpmax-eligible	0.0255%	3,920
Middle Eastern	0.0173%	5,778
Admixed American	0.014%	7,119
Ashkenazi Jewishnot grpmax-eligible	0.0139%	7,171
South Asian	0.0114%	8,775
East Asian	0.00698%	14,324
European (non-Finnish)	0.00442%	22,607
Remaining individualsnot grpmax-eligible	0.00328%	30,442

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.His461Pro
Coding: c.1382A>C
MANE Select: NM_018013
dbSNP: rs587780464
Type: single nucleotide variant
Location: chr6:107634226 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 52.41
Residue 461: 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-his461pro (accessed [today's date]).

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