Is FGFR3 p.Pro772= (c.2316G>A) pathogenic?

FGFR3 p.Pro772= (c.2316G>A) is classified Likely benign in FGFR3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-19). Ultra-rare (popmax 0.0165%, mid).

How common is FGFR3 p.Pro772= (c.2316G>A) in the general population?

FGFR3 p.Pro772= (c.2316G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

FGFR3 p.Pro772=

c.2316G>A · rs200629304 · VCV715119

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.26	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Overall
CADD	0.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,048 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00338% 54/1,599,928 alleles · ultra-rare exomes 47/1,447,670 · genomes 7/152,258 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0649%	1,542
Middle Easterngrpmax	0.0165%	6,048
Remaining individualsnot grpmax-eligible	0.00808%	12,382
South Asian	0.00788%	12,693
Admixed American	0.00682%	14,671
East Asian	0.00454%	22,048
African / African-American	0.00134%	74,720
European (non-Finnish)	0.00128%	78,268

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro772=
Coding: c.2316G>A
MANE Select: NM_000142
dbSNP: rs200629304
Type: single nucleotide variant
Location: chr4:1807157 (GRCh38)
Gene constraint: LOEUF 0.458 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.25 · 16 PDB
Residue 772: the 'disordered' region

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

Similar variants

FGFR3 p.Pro772Ala Uncertain significance ★★ ⚠ same residue
FGFR3 p.Pro772Leu Uncertain significance ★★ ⚠ 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-pro772 (accessed [today's date]).

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