Is GFER p.Arg23Pro (c.68G>C) pathogenic?

GFER p.Arg23Pro (c.68G>C) is classified Uncertain significance in GFER (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely benign (0.1312); Absent from gnomAD v4.1.

How common is GFER p.Arg23Pro (c.68G>C) in the general population?

GFER p.Arg23Pro (c.68G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GFER p.Arg23Pro (c.68G>C)?

AlphaMissense predicts likely benign (score 0.1312) — an in-silico prediction, not a clinical call.

GFER p.Arg23Pro

c.68G>C · rs2548268651 · VCV2429532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1312 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1312	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -6.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.2, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 1,806 bp · p 0.23 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GFER
Protein: p.Arg23Pro
Coding: c.68G>C
MANE Select: NM_005262
dbSNP: rs2548268651
Type: single nucleotide variant
Location: chr16:1984286 (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 23: 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-arg23pro (accessed [today's date]).

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