Is FGFR3 p.Arg196= (c.588C>T) pathogenic?

FGFR3 p.Arg196= (c.588C>T) is classified Benign in FGFR3 (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-06-01). Common (popmax 8.49%, afr) — too common for a highly-penetrant pathogenic allele; Associated with connective tissue disorder.

What condition is associated with FGFR3 p.Arg196= (c.588C>T)?

FGFR3 p.Arg196= (c.588C>T) is associated with connective tissue disorder (ClinVar).

FGFR3 p.Arg196=

Q: How common is FGFR3 p.Arg196= (c.588C>T) in the general population?

FGFR3 p.Arg196= (c.588C>T) is common (popmax 8.49%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.588C>T · rs2305180 · VCV197630

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Common

common (popmax 8.49%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

connective tissue disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.9	GERP -3
Overall
CADD	4.938	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49% African / African-American · 6,275/73,914 alleles

Filtering AF 8.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.24%

Overall 1.07% 16,804/1,563,482 alleles · common exomes 12,252/1,411,156 · genomes 4,552/152,326 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.49%	12
Middle Eastern	4.06%	25
Ashkenazi Jewishnot grpmax-eligible	2.69%	37
East Asian	2.5%	40
Amishnot grpmax-eligible	2.41%	41
South Asian	1.76%	57
Remaining individualsnot grpmax-eligible	1.61%	62
Admixed American	1.35%	74
European (non-Finnish)	0.452%	221
Finnishnot grpmax-eligible	0.0525%	1,904

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.Arg196=
Coding: c.588C>T
MANE Select: NM_000142
dbSNP: rs2305180
Type: single nucleotide variant
Location: chr4:1801509 (GRCh38)
Gene constraint: LOEUF 0.458 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.25 · 16 PDB
Residue 196: the ig-like c2-type 2 domain

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

Disease context

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FGFR3 p.Arg248Cys Pathogenic ★★ same condition
FGFR3 p.Gly380Arg Pathogenic ★★ same condition
FGFR3 p.Ser249Cys Pathogenic ★★ same condition
FGFR3 p.Ter807Ser Pathogenic ★★ same condition
FGFR3 p.Val271Met Uncertain significance ★★ ⚠ same condition
FGFR3 c.1075+5C>T Benign ★★ same condition
FGFR3 p.Arg116= Benign/Likely benign ★★ same condition
FGFR3 p.Asp139= Benign ★★ 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/fgfr3-p-arg196 (accessed [today's date]).

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