Is SOBP p.Pro326Ala (c.976C>G) pathogenic?

SOBP p.Pro326Ala (c.976C>G) is classified Uncertain significance in SOBP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely benign (0.0632); Ultra-rare (popmax 0.0252%, sas).

How common is SOBP p.Pro326Ala (c.976C>G) in the general population?

SOBP p.Pro326Ala (c.976C>G) is ultra-rare (popmax 0.0252%, sas) (gnomAD).

What do computational predictors say about SOBP p.Pro326Ala (c.976C>G)?

AlphaMissense predicts likely benign (score 0.0632) — an in-silico prediction, not a clinical call.

SOBP p.Pro326Ala

c.976C>G · VCV3321378

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0632 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0252%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0632	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -6.20	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 4.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 564 bp · p 0.0029 · regional, not allelic
Overall
CADD	20.8	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 0.0252% South Asian · 23/91,092 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00198% 32/1,614,004 alleles · ultra-rare exomes 31/1,461,828 · genomes 1/152,176 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0252%	3,961
European (non-Finnish)	0.000763%	131,114

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.Pro326Ala
Coding: c.976C>G
MANE Select: NM_018013
Type: single nucleotide variant
Location: chr6:107633820 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 52.41
Residue 326: the 'disordered' region

Full SOBP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SOBP p.Pro326Ser Uncertain significance ★ ⚠ same residue
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

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-pro326ala (accessed [today's date]).

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