Is FGFR1 p.Ser251Phe (c.752C>T) pathogenic?

FGFR1 p.Ser251Phe (c.752C>T) is classified Pathogenic in FGFR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-19). AlphaMissense: likely pathogenic (0.9754); Absent from gnomAD v4.1.

How common is FGFR1 p.Ser251Phe (c.752C>T) in the general population?

FGFR1 p.Ser251Phe (c.752C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FGFR1 p.Ser251Phe (c.752C>T)?

AlphaMissense predicts likely pathogenic (score 0.9754) — an in-silico prediction, not a clinical call.

FGFR1 p.Ser251Phe

c.752C>T · rs1064793120 · VCV418204

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9754 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9754	likely pathogenic ✓ concordant with ClinVar
REVEL	0.809	moderately pathogenic-leaning
SaProt	LLR -13.30	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 6,243 bp · p 6.1e-19 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FGFR1
Protein: p.Ser251Phe
Coding: c.752C>T
MANE Select: NM_023110
dbSNP: rs1064793120
Type: single nucleotide variant
Location: chr8:38424693 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.30 · 86 PDB

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

Similar variants

FGFR1 c.1977+1G>A Pathogenic/Likely pathogenic ★★ same type
FGFR1 c.1977+1G>T Pathogenic/Likely pathogenic ★★ same type
FGFR1 c.448+1G>A Likely pathogenic ★★ same type
FGFR1 c.449-6G>A Likely pathogenic ★★ same type
FGFR1 c.91+1G>A Pathogenic/Likely pathogenic ★★ same type
FGFR1 p.Ala343= Pathogenic/Likely pathogenic ★★ same type
FGFR1 p.Arg209Cys Likely pathogenic ★★ same type
FGFR1 p.Arg250Gln Pathogenic ★★ same type

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-ser251phe (accessed [today's date]).

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