Is SOBP p.Pro649= (c.1947G>A) pathogenic?

SOBP p.Pro649= (c.1947G>A) is classified Likely benign in SOBP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-01). Very rare (popmax 0.00329%, eas).

How common is SOBP p.Pro649= (c.1947G>A) in the general population?

SOBP p.Pro649= (c.1947G>A) is very rare (popmax 0.00329%, eas) (gnomAD).

SOBP p.Pro649=

c.1947G>A · rs774801789 · VCV2656819

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.72	GERP -1.2, phastCons 1
Overall
CADD	11.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% East Asian · 1/30,406 alleles

Overall 0.000143% 2/1,397,700 alleles · very rare exomes 2/1,246,934 · genomes 0/150,766 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00329%	30,406
South Asian	0.00148%	67,376

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.Pro649=
Coding: c.1947G>A
MANE Select: NM_018013
dbSNP: rs774801789
Type: single nucleotide variant
Location: chr6:107634791 (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

Similar variants

SOBP p.Pro649Leu 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-pro649 (accessed [today's date]).

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