Is FGFR3 p.Pro401Ala (c.1201C>G) pathogenic?

FGFR3 p.Pro401Ala (c.1201C>G) is classified Conflicting classifications of pathogenicity in FGFR3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0604); Ultra-rare (popmax 0.0217%, amr).

How common is FGFR3 p.Pro401Ala (c.1201C>G) in the general population?

FGFR3 p.Pro401Ala (c.1201C>G) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about FGFR3 p.Pro401Ala (c.1201C>G)?

AlphaMissense predicts likely benign (score 0.0604) — an in-silico prediction, not a clinical call.

FGFR3 p.Pro401Ala

c.1201C>G · rs762705505 · VCV2056854

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0604 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0604	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -5.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.56	GERP -2.9
Regional constraint	o/e 1.18	unconstrained · MANE · 2,931 bp · p 0.0092 · regional, not allelic
Overall
CADD	16.85	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 0.0217% Admixed American · 13/59,944 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00391% 63/1,612,840 alleles · ultra-rare exomes 60/1,460,632 · genomes 3/152,208 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,611
African / African-American	0.004%	24,973
European (non-Finnish)	0.0039%	25,647
Remaining individualsnot grpmax-eligible	0.0016%	62,452

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: FGFR3
Protein: p.Pro401Ala
Coding: c.1201C>G
MANE Select: NM_000142
dbSNP: rs762705505
Type: single nucleotide variant
Location: chr4:1804455 (GRCh38)
Gene constraint: LOEUF 0.458 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.25 · 16 PDB

Full FGFR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FGFR3 p.Pro401Ser Uncertain significance ★★ ⚠ same residue
FGFR3 p.Pro401Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
FGFR3 p.Ala391Glu Pathogenic ★★ same type
FGFR3 p.Arg248Cys Pathogenic ★★ same type
FGFR3 p.Arg621His Pathogenic/Likely pathogenic ★★ same type
FGFR3 p.Asn540Asp Pathogenic/Likely pathogenic ★★ same type
FGFR3 p.Asn540Lys Pathogenic ★★ same type
FGFR3 p.Asn540Ser Pathogenic/Likely 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/fgfr3-p-pro401ala (accessed [today's date]).

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