Is SELENON p.Phe175Ser (c.524T>C) pathogenic?

SELENON p.Phe175Ser (c.524T>C) is classified Uncertain significance in SELENON (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SELENON p.Phe175Ser (c.524T>C)?

SELENON p.Phe175Ser (c.524T>C) is associated with Inborn genetic diseases (ClinVar).

How common is SELENON p.Phe175Ser (c.524T>C) in the general population?

SELENON p.Phe175Ser (c.524T>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

SELENON p.Phe175Ser

c.524T>C · VCV3793976

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.85	moderately pathogenic-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,952 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,010 alleles · very rare exomes 2/1,461,782 · genomes 0/152,228 · joint denominator

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: SELENON
Protein: p.Phe175Ser
Coding: c.524T>C
MANE Select: NM_206926
Type: single nucleotide variant
Location: chr1:25808668 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI <0.01 (gnomAD)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SELENON p.Phe175Val Uncertain significance ★ same residue
SELENON p.Phe175= Likely benign ★ same residue
SELENON p.Ala150Thr Uncertain significance ★★ same condition
SELENON p.Ala160Thr Uncertain significance ★★ same condition
SELENON p.Ala160Val Uncertain significance ★★ same condition
SELENON p.Ala22Val Uncertain significance ★★ same condition
SELENON p.Ala478Val Uncertain significance ★★ same condition
SELENON p.Ala4Pro 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/selenon-p-phe175ser (accessed [today's date]).

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