Is FGF9 p.Pro26Arg (c.77C>G) pathogenic?

FGF9 p.Pro26Arg (c.77C>G) is classified Uncertain significance in FGF9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely benign (0.1726); Very rare (popmax 0.000254%, nfe).

How common is FGF9 p.Pro26Arg (c.77C>G) in the general population?

FGF9 p.Pro26Arg (c.77C>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about FGF9 p.Pro26Arg (c.77C>G)?

AlphaMissense predicts likely benign (score 0.1726) — an in-silico prediction, not a clinical call.

FGF9 p.Pro26Arg

c.77C>G · rs1871779721 · VCV1473856

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1726 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1726	likely benign
REVEL	0.353	indeterminate
SaProt	LLR -7.29	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 171 bp · p 0.59 · regional, not allelic
Overall
CADD	25.4	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 0.000254% European (non-Finnish) · 3/1,180,036 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,166 alleles · very rare exomes 3/1,461,886 · genomes 0/152,280 · joint denominator

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: FGF9
Protein: p.Pro26Arg
Coding: c.77C>G
MANE Select: NM_002010
dbSNP: rs1871779721
Type: single nucleotide variant
Location: chr13:21671989 (GRCh38)
Gene constraint: LOEUF 0.418 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 84.19 · 3 PDB

Full FGF9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FGF9 p.Pro26Ser Uncertain significance ★ ⚠ same residue
FGF9 p.Asp35Gly Uncertain significance ★★ ⚠ same type
FGF9 p.Pro30Ser Uncertain significance ★★ ⚠ same type
FGF9 c.278-14C>T Benign ★★ same type
FGF9 c.278-28T>C Benign ★★ same type
FGF9 c.381+116T>C Benign ★★ same type
FGF9 c.381+17C>T Benign ★★ same type
FGF9 c.-171A>G Benign ★★ 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/fgf9-p-pro26arg (accessed [today's date]).

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