Is FGFR1 p.Pro802= (c.2406C>T) pathogenic?

FGFR1 p.Pro802= (c.2406C>T) is classified Likely benign in FGFR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-24). Very rare (popmax 0.00446%, eas); Associated with hypogonadotropic hypogonadism 2 with or without anosmia.

What condition is associated with FGFR1 p.Pro802= (c.2406C>T)?

FGFR1 p.Pro802= (c.2406C>T) is associated with hypogonadotropic hypogonadism 2 with or without anosmia, Pfeiffer syndrome (ClinVar).

How common is FGFR1 p.Pro802= (c.2406C>T) in the general population?

FGFR1 p.Pro802= (c.2406C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

FGFR1 p.Pro802=

c.2406C>T · rs573344794 · VCV1456608

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

hypogonadotropic hypogonadism 2 with or without anosmia

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 -4.1	GERP -4.7
Overall
CADD	2.972	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,856 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000744% 12/1,613,500 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,428
African / African-American	0.00133%	74,914
South Asian	0.0011%	91,030
European (non-Finnish)	0.000678%	147,482

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.Pro802=
Coding: c.2406C>T
MANE Select: NM_023110
dbSNP: rs573344794
Type: single nucleotide variant
Location: chr8:38413691 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.30 · 86 PDB
Residue 802: the 'disordered' region; a UniProt-annotated variant site (in hh2)

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

Disease context

hypogonadotropic hypogonadism 2 with or without anosmia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Pfeiffer 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-pro802 (accessed [today's date]).

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