Is FGF12 p.Pro6= (c.18C>T) pathogenic?

FGF12 p.Pro6= (c.18C>T) is classified Likely benign in FGF12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). Very rare (popmax 8.49e-05%, nfe).

How common is FGF12 p.Pro6= (c.18C>T) in the general population?

FGF12 p.Pro6= (c.18C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

FGF12 p.Pro6=

c.18C>T · VCV3652413

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1
Overall
CADD	12.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,964 alleles

Overall 6.2e-05% 1/1,611,674 alleles · very rare exomes 1/1,459,502 · genomes 0/152,172 · joint denominator

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: FGF12
Protein: p.Pro6=
Coding: c.18C>T
MANE Select: NM_004113
Type: single nucleotide variant
Location: chr3:192360534 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI 0.15 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.91 · 2 PDB
Residue 6: the 'disordered' region

Full FGF12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FGF12 p.Arg52His Pathogenic/Likely pathogenic ★★ same type
FGF12 p.Gly50Ser Pathogenic/Likely pathogenic ★★ same type
FGF12 c.125-3C>G Uncertain significance ★★ same type
FGF12 c.14-47513G>T Uncertain significance ★★ ⚠ same type
FGF12 c.14-47520A>G Uncertain significance ★★ ⚠ same type
FGF12 c.14-47558G>C Uncertain significance ★★ ⚠ same type
FGF12 c.14-47562G>A Uncertain significance ★★ same type
FGF12 c.14-47655C>T 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/fgf12-p-pro6 (accessed [today's date]).

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