Is FGFR1 p.Asp69= (c.207C>T) pathogenic?

FGFR1 p.Asp69= (c.207C>T) is classified Likely benign in FGFR1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-10-17). Very rare (popmax 0.00446%, eas); Associated with hypogonadotropic hypogonadism 2 with or without anosmia.

What condition is associated with FGFR1 p.Asp69= (c.207C>T)?

FGFR1 p.Asp69= (c.207C>T) is associated with hypogonadotropic hypogonadism 2 with or without anosmia, Pfeiffer syndrome (ClinVar).

How common is FGFR1 p.Asp69= (c.207C>T) in the general population?

FGFR1 p.Asp69= (c.207C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

FGFR1 p.Asp69=

c.207C>T · rs145220136 · VCV2658551

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 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 1.8	GERP -1.6, phastCons 1
Overall
CADD	14.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,880 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00173% 28/1,613,854 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,440
South Asian	0.00439%	22,763
Remaining individualsnot grpmax-eligible	0.0032%	31,235
European (non-Finnish)	0.00169%	58,999

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.Asp69=
Coding: c.207C>T
MANE Select: NM_023110
dbSNP: rs145220136
Type: single nucleotide variant
Location: chr8:38429833 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.30 · 86 PDB
Residue 69: a β-strand; a disulfide bond; the ig-like c2-type 1 domain

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.Asp69Asn 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
FGFR1 p.Arg250Gln 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-asp69 (accessed [today's date]).

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