Is FGF10 p.Cys20Ser (c.58T>A) pathogenic?

FGF10 p.Cys20Ser (c.58T>A) is classified Uncertain significance in FGF10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-27). AlphaMissense: likely benign (0.1019); Very rare (popmax 0.00167%, amr); Associated with aplasia of lacrimal and salivary glands.

What condition is associated with FGF10 p.Cys20Ser (c.58T>A)?

FGF10 p.Cys20Ser (c.58T>A) is associated with aplasia of lacrimal and salivary glands, lacrimoauriculodentodigital syndrome 3 (ClinVar).

How common is FGF10 p.Cys20Ser (c.58T>A) in the general population?

FGF10 p.Cys20Ser (c.58T>A) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Aplasia of lacrimal and salivary glands inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FGF10 p.Cys20Ser (c.58T>A)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

FGF10 p.Cys20Ser

c.58T>A · VCV3592699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

aplasia of lacrimal and salivary glands

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -8.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.88, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 211 bp · p 0.42 · regional, not allelic
Overall
CADD	15.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,026 alleles

Overall 6.84e-05% 1/1,461,882 alleles · very rare

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: FGF10
Protein: p.Cys20Ser
Coding: c.58T>A
MANE Select: NM_004465
Type: single nucleotide variant
Location: chr5:44388625 (GRCh38)
Gene constraint: LOEUF 0.267 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.12 · 2 PDB

Full FGF10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

aplasia of lacrimal and salivary glands — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lacrimoauriculodentodigital syndrome 3

For Aplasia of lacrimal and salivary glands (Orphanet):

Inheritance: Autosomal dominant

Similar variants

FGF10 p.Cys20= Likely benign ★ same residue
FGF10 p.Arg193Ter Pathogenic/Likely pathogenic ★★ same condition
FGF10 p.Val123Ile Uncertain significance ★★ ⚠ same condition
FGF10 p.Val205Met Uncertain significance ★★ ⚠ same condition
FGF10 c.430-15G>C Benign ★★ same condition
FGF10 p.His207Pro Benign/Likely benign ★★ same condition
FGF10 p.Thr197= Benign ★★ same condition
FGF10 p.Val33Ile Benign/Likely benign ★★ 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/fgf10-p-cys20ser (accessed [today's date]).

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