Is FGFR1 p.Pro466= (c.1398C>T) pathogenic?

FGFR1 p.Pro466= (c.1398C>T) is classified Benign/Likely benign in FGFR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-12). Rare (popmax 0.125%, afr); Associated with osteoglophonic dysplasia.

What condition is associated with FGFR1 p.Pro466= (c.1398C>T)?

FGFR1 p.Pro466= (c.1398C>T) is associated with osteoglophonic dysplasia, Pfeiffer syndrome, Jackson-Weiss syndrome (ClinVar).

How common is FGFR1 p.Pro466= (c.1398C>T) in the general population?

FGFR1 p.Pro466= (c.1398C>T) is rare (popmax 0.125%, afr) (gnomAD).

FGFR1 p.Pro466=

c.1398C>T · rs150652786 · VCV1168531

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.125%, afr)

Conditions

osteoglophonic dysplasia

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 -9.3	GERP -4.9
Overall
CADD	1.046	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.125% African / African-American · 94/75,072 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.097%

Overall 0.00774% 125/1,614,200 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.125%	799
Admixed American	0.00833%	12,005
Remaining individualsnot grpmax-eligible	0.008%	12,502
East Asian	0.00446%	22,440
South Asian	0.0022%	45,541
European (non-Finnish)	0.00144%	69,414

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: FGFR1
Protein: p.Pro466=
Coding: c.1398C>T
MANE Select: NM_023110
dbSNP: rs150652786
Type: single nucleotide variant
Location: chr8:38418260 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.30 · 86 PDB
Residue 466: an α-helix; a UniProt-annotated variant site (in hh2)

Full FGFR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

osteoglophonic dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Pfeiffer syndrome Jackson-Weiss syndrome hypogonadotropic hypogonadism 2 with or without anosmia trigonocephaly 1 encephalocraniocutaneous lipomatosis Hartsfield-Bixler-Demyer syndrome

Similar variants

FGFR1 c.1977+1G>A Pathogenic/Likely pathogenic ★★ same condition
FGFR1 c.1977+1G>T Pathogenic/Likely pathogenic ★★ same condition
FGFR1 c.448+1G>A Likely pathogenic ★★ same condition
FGFR1 c.449-6G>A Likely pathogenic ★★ same condition
FGFR1 c.91+1G>A Pathogenic/Likely pathogenic ★★ same condition
FGFR1 p.Arg209Cys Likely pathogenic ★★ same condition
FGFR1 p.Arg250Gln Pathogenic ★★ same condition
FGFR1 p.Arg250Trp Pathogenic/Likely pathogenic ★★ 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/fgfr1-p-pro466 (accessed [today's date]).

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