Is FGF8 p.Ser58Pro (c.172T>C) pathogenic?

FGF8 p.Ser58Pro (c.172T>C) is classified Uncertain significance in FGF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FGF8 p.Ser58Pro (c.172T>C)?

FGF8 p.Ser58Pro (c.172T>C) is associated with Inborn genetic diseases (ClinVar).

How common is FGF8 p.Ser58Pro (c.172T>C) in the general population?

FGF8 p.Ser58Pro (c.172T>C) is absent from gnomAD v4.1 (gnomAD).

FGF8 p.Ser58Pro

c.172T>C · VCV3278654

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.165	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 5,291 bp · p 0.0067 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FGF8
Protein: p.Ser58Pro
Coding: c.172T>C
MANE Select: NM_033163
Type: single nucleotide variant
Location: chr10:101774897 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 81.34 · 1 PDB

Full FGF8 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

FGF8 p.Ala147Thr Uncertain significance ★★ ⚠ same condition
FGF8 p.Arg195Trp Uncertain significance ★★ ⚠ same condition
FGF8 p.Arg233Cys Uncertain significance ★★ ⚠ same condition
FGF8 p.Thr72= Benign/Likely benign ★★ same condition
FGF8 p.Ala7Gly Uncertain significance ★ ⚠ same condition
FGF8 p.Arg129Gln Uncertain significance ★ ⚠ same condition
FGF8 p.Arg129Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
FGF8 p.Arg189Cys 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/fgf8-p-ser58pro (accessed [today's date]).

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