Is FGF9 p.Ser149= (c.447A>G) pathogenic?

FGF9 p.Ser149= (c.447A>G) is classified Benign in FGF9 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 97.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with multiple synostoses syndrome 3.

What condition is associated with FGF9 p.Ser149= (c.447A>G)?

FGF9 p.Ser149= (c.447A>G) is associated with multiple synostoses syndrome 3 (ClinVar).

FGF9 p.Ser149=

Q: How common is FGF9 p.Ser149= (c.447A>G) in the general population?

FGF9 p.Ser149= (c.447A>G) is common (popmax 97.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.447A>G · rs9509841 · VCV311424

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 97.5%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

multiple synostoses syndrome 3

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 0.14	GERP -5.4, phastCons 0.73
Overall
CADD	5.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 97.5% East Asian · 43,713/44,850 alleles

Filtering AF 96.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 96.4%

Overall 82.9% 1,337,665/1,613,372 alleles · common exomes 1,217,008/1,461,460 · genomes 120,657/151,912 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	97.5%	1
Admixed American	90.4%	1
South Asian	89.9%	1
Middle Eastern	85.9%	1
Ashkenazi Jewishnot grpmax-eligible	84.6%	1
Amishnot grpmax-eligible	84.3%	1
Remaining individualsnot grpmax-eligible	82.7%	1
European (non-Finnish)	82.6%	1
Finnishnot grpmax-eligible	80.8%	1
African / African-American	66%	2

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.Ser149=
Coding: c.447A>G
MANE Select: NM_002010
dbSNP: rs9509841
Type: single nucleotide variant
Location: chr13:21701255 (GRCh38)
Gene constraint: LOEUF 0.418 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 84.19 · 3 PDB
Residue 149: a β-strand

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

Disease context

multiple synostoses syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FGF9 c.278-14C>T Benign ★★ same condition
FGF9 c.381+17C>T Benign ★★ same condition
FGF9 c.-171A>G Benign ★★ same condition
FGF9 c.*1094C>T Benign ★★ same condition
FGF9 c.*208G>A Benign ★★ same condition
FGF9 c.*2563G>C Benign ★★ same condition
FGF9 c.*2585C>T Benign ★★ same condition
FGF9 c.*2634C>T 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/fgf9-p-ser149 (accessed [today's date]).

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