Is FGFR1 p.Pro150= (c.450C>T) pathogenic?

FGFR1 p.Pro150= (c.450C>T) is classified Likely benign in FGFR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). Ultra-rare (popmax 0.0117%, amr); Associated with hypogonadotropic hypogonadism 2 with or without anosmia.

What condition is associated with FGFR1 p.Pro150= (c.450C>T)?

FGFR1 p.Pro150= (c.450C>T) is associated with hypogonadotropic hypogonadism 2 with or without anosmia, Pfeiffer syndrome (ClinVar).

How common is FGFR1 p.Pro150= (c.450C>T) in the general population?

FGFR1 p.Pro150= (c.450C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

FGFR1 p.Pro150=

c.450C>T · rs766091702 · VCV1613884

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

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	<0.2	all four deltas below 0.2 · G>T here scores Δ0.93 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.6	GERP -0.83, phastCons 1
Overall
CADD	14.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,016 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000744% 12/1,613,958 alleles · ultra-rare exomes 10/1,461,738 · genomes 2/152,220 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,574
South Asian	0.0011%	91,074
European (non-Finnish)	0.000339%	295,011

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.Pro150=
Coding: c.450C>T
MANE Select: NM_023110
dbSNP: rs766091702
Type: single nucleotide variant
Location: chr8:38428092 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.30 · 86 PDB
Residue 150: the 'disordered' region

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 p.Pro150Ser Uncertain significance ★★ ⚠ same residue
FGFR1 p.Pro150His Uncertain significance ★ ⚠ same residue
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

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-pro150 (accessed [today's date]).

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