Is FGFR1 p.Ser96= (c.288C>T) pathogenic?

FGFR1 p.Ser96= (c.288C>T) is classified Likely benign in FGFR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-02). Very rare (popmax 0.00228%, eas); Associated with Pfeiffer syndrome.

What condition is associated with FGFR1 p.Ser96= (c.288C>T)?

FGFR1 p.Ser96= (c.288C>T) is associated with Pfeiffer syndrome, hypogonadotropic hypogonadism 2 with or without anosmia (ClinVar).

How common is FGFR1 p.Ser96= (c.288C>T) in the general population?

FGFR1 p.Ser96= (c.288C>T) is very rare (popmax 0.00228%, eas) (gnomAD).

FGFR1 p.Ser96=

c.288C>T · rs757362905 · VCV1543290

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00228%, eas)

Conditions

Pfeiffer syndrome

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 -3.1	GERP -4.7
Overall
CADD	8.111	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00228% East Asian · 1/43,862 alleles

Filtering AF 0.00096% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000792%

Overall 0.00144% 23/1,596,788 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00228%	43,862
South Asian	0.00226%	44,228
Admixed American	0.00173%	57,772
European (non-Finnish)	0.00154%	65,091
African / African-American	0.00134%	74,542

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.Ser96=
Coding: c.288C>T
MANE Select: NM_023110
dbSNP: rs757362905
Type: single nucleotide variant
Location: chr8:38429752 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.30 · 86 PDB
Residue 96: a disulfide bond; the ig-like c2-type 1 domain; a UniProt-annotated variant site (in hh2; uncertain significance)

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

Disease context

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

Also linked: hypogonadotropic hypogonadism 2 with or without anosmia

Similar variants

FGFR1 p.Ser96Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
FGFR1 p.Ser96Pro Uncertain significance ★ ⚠ same residue
FGFR1 p.Ser96Phe 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

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-ser96 (accessed [today's date]).

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