Is SOX17 p.Phe183= (c.549C>T) pathogenic?

SOX17 p.Phe183= (c.549C>T) is classified Likely benign in SOX17 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-24). Very rare (popmax 0.00975%, nfe); Associated with vesicoureteral reflux 3.

What condition is associated with SOX17 p.Phe183= (c.549C>T)?

SOX17 p.Phe183= (c.549C>T) is associated with vesicoureteral reflux 3 (ClinVar).

How common is SOX17 p.Phe183= (c.549C>T) in the general population?

SOX17 p.Phe183= (c.549C>T) is very rare (popmax 0.00975%, nfe) (gnomAD).

SOX17 p.Phe183=

c.549C>T · rs929689090 · VCV762739

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00975%, nfe)

Conditions

vesicoureteral reflux 3

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 0.06	GERP -1.8, phastCons 0.77
Overall
CADD	6.145	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00975% European (non-Finnish) · 111/1,138,296 alleles

Filtering AF 0.0082% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00771%

Overall 0.00772% 117/1,515,348 alleles · very rare exomes 109/1,363,172 · genomes 8/152,176 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00975%	10,255
Remaining individualsnot grpmax-eligible	0.00681%	14,678
African / African-American	0.00289%	34,639

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: SOX17
Protein: p.Phe183=
Coding: c.549C>T
MANE Select: NM_022454
dbSNP: rs929689090
Type: single nucleotide variant
Location: chr8:54459299 (GRCh38)
Gene constraint: LOEUF 0.614 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 58.95 · 2 PDB
Residue 183: a UniProt-annotated variant site (in pph7; pathogenic); a UniProt-annotated variant site (in pph7; pathogenic; contrary to the wild type, the mutant does not transcriptionally activate its target gene notch1); a UniProt-annotated variant site (in pph7; likely pathogenic)

Full SOX17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

vesicoureteral reflux 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SOX17 p.Arg138Pro Likely pathogenic ★★ same condition
SOX17 p.Ala292Val Uncertain significance ★★ ⚠ same condition
SOX17 p.Ala305Thr Uncertain significance ★★ ⚠ same condition
SOX17 p.Ala56Asp Uncertain significance ★★ ⚠ same condition
SOX17 p.Cys371Trp Uncertain significance ★★ ⚠ same condition
SOX17 p.Gly301Asp Uncertain significance ★★ ⚠ same condition
SOX17 p.His319Arg Uncertain significance ★★ ⚠ same condition
SOX17 p.Leu167Val Uncertain significance ★★ ⚠ 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/sox17-p-phe183 (accessed [today's date]).

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