Is FGF20 p.Ala48= (c.144G>C) pathogenic?

FGF20 p.Ala48= (c.144G>C) is classified Benign in FGF20 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 99.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with renal hypodysplasia/aplasia 2.

What condition is associated with FGF20 p.Ala48= (c.144G>C)?

FGF20 p.Ala48= (c.144G>C) is associated with renal hypodysplasia/aplasia 2 (ClinVar).

FGF20 p.Ala48=

Q: How common is FGF20 p.Ala48= (c.144G>C) in the general population?

FGF20 p.Ala48= (c.144G>C) is common (popmax 99.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.144G>C · rs10448135 · VCV1246783

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 99.9%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

renal hypodysplasia/aplasia 2

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 0.15	GERP -4.7, phastCons 0.92
Overall
CADD	6.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 99.9% East Asian · 32,688/32,736 alleles

Filtering AF 98.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.6%

Overall 76.9% 1,099,594/1,430,044 alleles · common exomes 976,112/1,278,256 · genomes 123,482/151,788 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	99.9%	1
African / African-American	90.8%	1
Admixed American	85.4%	1
Amishnot grpmax-eligible	82.3%	1
South Asian	79.3%	1
Remaining individualsnot grpmax-eligible	77.8%	1
Finnishnot grpmax-eligible	76.8%	1
European (non-Finnish)	75%	1
Middle Eastern	74.7%	1
Ashkenazi Jewishnot grpmax-eligible	72.6%	1

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.Ala48=
Coding: c.144G>C
MANE Select: NM_019851
dbSNP: rs10448135
Type: single nucleotide variant
Location: chr8:17001889 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 83.52 · 1 PDB
Residue 48: the 'disordered' region

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

Disease context

renal hypodysplasia/aplasia 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FGF20 p.Ala48Ser Uncertain significance ★ ⚠ same residue
FGF20 p.Ala48Val Uncertain significance ★ ⚠ same residue
FGF20 c.391-1G>A Likely pathogenic ★ same condition
FGF20 p.Val113fs Pathogenic same condition
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

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-ala48 (accessed [today's date]).

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