Is FGFR1 p.Pro772Ser (c.2314C>T) pathogenic?

FGFR1 p.Pro772Ser (c.2314C>T) is classified Benign/Likely benign in FGFR1 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1137); Low-frequency (popmax 4.27%, afr); Associated with Pfeiffer syndrome.

What condition is associated with FGFR1 p.Pro772Ser (c.2314C>T)?

FGFR1 p.Pro772Ser (c.2314C>T) is associated with Pfeiffer syndrome, hypogonadotropic hypogonadism 2 with or without anosmia, osteoglophonic dysplasia (ClinVar).

How common is FGFR1 p.Pro772Ser (c.2314C>T) in the general population?

FGFR1 p.Pro772Ser (c.2314C>T) is low-frequency (popmax 4.27%, afr) (gnomAD).

What do computational predictors say about FGFR1 p.Pro772Ser (c.2314C>T)?

AlphaMissense predicts likely benign (score 0.1137) — an in-silico prediction, not a clinical call.

FGFR1 p.Pro772Ser

c.2314C>T · rs56234888 · VCV194891

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.1137 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.27%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Pfeiffer syndrome

Computational evidence

Protein change
AlphaMissense	0.1137	likely benign
REVEL	0.417	indeterminate
SaProt	LLR -11.48	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 326 bp · p 0.064 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.27% African / African-American · 3,200/75,022 alleles

Filtering AF 4.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.09%

Overall 0.224% 3,617/1,614,080 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.27%	23
Remaining individualsnot grpmax-eligible	0.318%	314
Admixed American	0.23%	435
Middle Eastern	0.182%	551
South Asian	0.00659%	15,180
European (non-Finnish)	0.00534%	18,730

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.Pro772Ser
Coding: c.2314C>T
MANE Select: NM_023110
dbSNP: rs56234888
Type: single nucleotide variant
Location: chr8:38413783 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.30 · 86 PDB
Residue 772: a UniProt-annotated variant site (in hh2); a UniProt-annotated variant site (in)

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 osteoglophonic dysplasia trigonocephaly 1 craniosynostosis

Similar variants

FGFR1 p.Pro772Thr 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-pro772ser (accessed [today's date]).

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