Is GFER p.Phe16= (c.48C>T) pathogenic?

GFER p.Phe16= (c.48C>T) is classified Likely benign in GFER (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-12). Very rare (popmax 0.000267%, nfe).

How common is GFER p.Phe16= (c.48C>T) in the general population?

GFER p.Phe16= (c.48C>T) is very rare (popmax 0.000267%, nfe) (gnomAD).

GFER p.Phe16=

c.48C>T · VCV3691918

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000267%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	10.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000267% European (non-Finnish) · 3/1,122,798 alleles

Filtering AF 7.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000203% 3/1,480,444 alleles · very rare exomes 3/1,328,260 · genomes 0/152,184 · 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: GFER
Protein: p.Phe16=
Coding: c.48C>T
MANE Select: NM_005262
Type: single nucleotide variant
Location: chr16:1984266 (GRCh38)
Gene constraint: LOEUF 1.87 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.50 · 7 PDB
Residue 16: the 'disordered' region

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

Similar variants

GFER p.Arg194His Pathogenic ★★ same type
GFER p.Ser189Ter Pathogenic ★★ same type
GFER c.258+1G>A Uncertain significance ★★ same type
GFER p.Ala45Thr Uncertain significance ★★ ⚠ same type
GFER p.Ala46Val Uncertain significance ★★ ⚠ same type
GFER p.Ala73Ser Uncertain significance ★★ ⚠ same type
GFER p.Arg196Cys Uncertain significance ★★ ⚠ same type
GFER p.Arg82Gln 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/gfer-p-phe16 (accessed [today's date]).

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