Is FGF10 p.Arg80Ser (c.240A>C) pathogenic?

FGF10 p.Arg80Ser (c.240A>C) is classified Conflicting classifications of pathogenicity in FGF10 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-05-04). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1; Associated with LADD syndrome.

What condition is associated with FGF10 p.Arg80Ser (c.240A>C)?

FGF10 p.Arg80Ser (c.240A>C) is associated with LADD syndrome, aplasia of lacrimal and salivary glands (ClinVar).

How common is FGF10 p.Arg80Ser (c.240A>C) in the general population?

FGF10 p.Arg80Ser (c.240A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FGF10 p.Arg80Ser (c.240A>C)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

FGF10 p.Arg80Ser

c.240A>C · rs104893888 · VCV7534

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

LADD syndrome

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic · top 1% in FGF10
REVEL	0.884	moderately pathogenic-leaning
SaProt	LLR -14.57	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.18	GERP -3.6, phastCons 0.64
Regional constraint	o/e 0.61	unconstrained · MANE · 83 kb · p 8.2e-07 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

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

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: FGF10
Protein: p.Arg80Ser
Coding: c.240A>C
MANE Select: NM_004465
dbSNP: rs104893888
Type: single nucleotide variant
Location: chr5:44388443 (GRCh38)
Gene constraint: LOEUF 0.267 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.12 · 2 PDB
Residue 80: a β-strand

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

Disease context

LADD syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: aplasia of lacrimal and salivary glands

Similar variants

FGF10 p.Arg193Ter Pathogenic/Likely pathogenic ★★ same condition
FGF10 p.Gly64Ter Pathogenic ★★ same condition
FGF10 p.Asn181His Uncertain significance ★★ ⚠ 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

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-arg80ser (accessed [today's date]).

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