Is FGF12 p.Pro48= (c.144C>T) pathogenic?

FGF12 p.Pro48= (c.144C>T) is classified Likely benign in FGF12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-19). Very rare (popmax 0.00334%, amr).

How common is FGF12 p.Pro48= (c.144C>T) in the general population?

FGF12 p.Pro48= (c.144C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

FGF12 p.Pro48=

c.144C>T · rs201446852 · VCV2882884

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

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 -4.6	GERP -4.4
Overall
CADD	0.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,868 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00112% 18/1,612,524 alleles · very rare exomes 16/1,460,382 · genomes 2/152,142 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,934
South Asian	0.0022%	45,508
African / African-American	0.00133%	74,958
European (non-Finnish)	0.0011%	90,685

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.Pro48=
Coding: c.144C>T
MANE Select: NM_004113
dbSNP: rs201446852
Type: single nucleotide variant
Location: chr3:192335445 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI 0.15 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.91 · 2 PDB

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

Similar variants

FGF12 p.Pro48Ser Uncertain significance ★ ⚠ same residue
FGF12 p.Pro48Leu Likely benign ★ same residue
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

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-pro48 (accessed [today's date]).

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