Is FGF9 p.Pro172Ser (c.514C>T) pathogenic?

FGF9 p.Pro172Ser (c.514C>T) is classified Uncertain significance in FGF9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-20). AlphaMissense: ambiguous (0.3797); Very rare (popmax 0.000593%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FGF9 p.Pro172Ser (c.514C>T)?

FGF9 p.Pro172Ser (c.514C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FGF9 p.Pro172Ser (c.514C>T) in the general population?

FGF9 p.Pro172Ser (c.514C>T) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about FGF9 p.Pro172Ser (c.514C>T)?

AlphaMissense predicts ambiguous (score 0.3797) — an in-silico prediction, not a clinical call.

FGF9 p.Pro172Ser

c.514C>T · rs776618974 · VCV2527216

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3797 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3797	ambiguous
REVEL	0.567	indeterminate
SaProt	LLR -10.11	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 29 kb · p 2.5e-06 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,974 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,780 alleles · very rare exomes 6/1,461,886 · genomes 1/151,894 · 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.Pro172Ser
Coding: c.514C>T
MANE Select: NM_002010
dbSNP: rs776618974
Type: single nucleotide variant
Location: chr13:21701322 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FGF9 p.Pro172= Likely benign ★★ same residue
FGF9 p.Asp35Gly Uncertain significance ★★ ⚠ same condition
FGF9 p.Pro30Ser Uncertain significance ★★ ⚠ same condition
FGF9 p.Ala42Val Uncertain significance ★ ⚠ same condition
FGF9 p.Asn119Ser Uncertain significance ★ ⚠ same condition
FGF9 p.Glu123Val Uncertain significance ★ same condition
FGF9 p.Gly38Ala Uncertain significance ★ ⚠ same condition
FGF9 p.Pro26Ser Uncertain significance ★ ⚠ 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/fgf9-p-pro172ser (accessed [today's date]).

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