Is FGF20 p.Pro34= (c.102G>A) pathogenic?

FGF20 p.Pro34= (c.102G>A) is classified Benign/Likely benign in FGF20 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Common (popmax 17.2%, nfe) — too common for a highly-penetrant pathogenic allele.

FGF20 p.Pro34=

Q: How common is FGF20 p.Pro34= (c.102G>A) in the general population?

FGF20 p.Pro34= (c.102G>A) is common (popmax 17.2%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.102G>A · rs17514894 · VCV1231868

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 17.2%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.55	GERP -0.77, phastCons 0.003
Overall
CADD	9.994	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.2% European (non-Finnish) · 193,109/1,122,244 alleles

Filtering AF 17.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.1%

Overall 15.7% 234,017/1,492,346 alleles · common exomes 215,167/1,340,382 · genomes 18,850/151,964 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	18.5%	5
European (non-Finnish)grpmax	17.2%	6
Remaining individualsnot grpmax-eligible	15.1%	7
Middle Eastern	14.6%	7
Finnishnot grpmax-eligible	14.2%	7
South Asian	13.5%	7
Amishnot grpmax-eligible	9.76%	10
Admixed American	8.75%	11
African / African-American	5.78%	17
East Asian	0.111%	901

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: FGF20
Protein: p.Pro34=
Coding: c.102G>A
MANE Select: NM_019851
dbSNP: rs17514894
Type: single nucleotide variant
Location: chr8:17001931 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 83.52 · 1 PDB
Residue 34: the 'disordered' region

Full FGF20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FGF20 p.Pro34Thr Uncertain significance same residue
FGF20 p.Ala179Ser Uncertain significance ★★ ⚠ same type
FGF20 p.Ala55Thr Uncertain significance ★★ ⚠ same type
FGF20 p.Arg41Gly Uncertain significance ★★ ⚠ same type
FGF20 p.Gln20Leu Uncertain significance ★★ ⚠ same type
FGF20 p.Glu45Gly Uncertain significance ★★ ⚠ same type
FGF20 p.Gly16Cys Uncertain significance ★★ ⚠ same type
FGF20 p.Gly50Ser 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/fgf20-p-pro34 (accessed [today's date]).

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