Is FGF1 p.Arg134Pro (c.401G>C) pathogenic?

FGF1 p.Arg134Pro (c.401G>C) is classified Uncertain significance in FGF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely benign (0.1834); Ultra-rare (popmax 0.0105%, nfe).

How common is FGF1 p.Arg134Pro (c.401G>C) in the general population?

FGF1 p.Arg134Pro (c.401G>C) is ultra-rare (popmax 0.0105%, nfe) (gnomAD).

What do computational predictors say about FGF1 p.Arg134Pro (c.401G>C)?

AlphaMissense predicts likely benign (score 0.1834) — an in-silico prediction, not a clinical call.

FGF1 p.Arg134Pro

c.401G>C · rs145843967 · VCV2360481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1834 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0105%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1834	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -6.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.8, phastCons 0.8
Regional constraint	o/e 0.81	unconstrained · MANE · 19 kb · p 0.0083 · regional, not allelic
Overall
CADD	16.24	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0105% European (non-Finnish) · 124/1,179,946 alleles

Filtering AF 0.00901% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00842%

Overall 0.00799% 129/1,613,928 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0105%	9,516
Remaining individualsnot grpmax-eligible	0.0064%	15,619
African / African-American	0.00133%	74,916

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: FGF1
Protein: p.Arg134Pro
Coding: c.401G>C
MANE Select: NM_000800
dbSNP: rs145843967
Type: single nucleotide variant
Location: chr5:142595357 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 91.05 · 96 PDB
Residue 134: the 'heparin-binding' region

Full FGF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FGF1 p.Ala118Pro Uncertain significance ★ ⚠ same type
FGF1 p.Arg137Gln Uncertain significance ★ ⚠ same type
FGF1 p.Asp47Gly Uncertain significance ★ ⚠ same type
FGF1 p.Cys132Gly Uncertain significance ★ ⚠ same type
FGF1 p.Gln78Arg Uncertain significance ★ ⚠ same type
FGF1 p.Glu14Gln Uncertain significance ★ ⚠ same type
FGF1 p.Glu96Gly Uncertain significance ★ ⚠ same type
FGF1 p.Gly34Arg Uncertain significance ★ ⚠ 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/fgf1-p-arg134pro (accessed [today's date]).

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