Is GFER p.Pro19Ser (c.55C>T) pathogenic?

GFER p.Pro19Ser (c.55C>T) is classified Uncertain significance in GFER (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-26). AlphaMissense: likely benign (0.2142); Ultra-rare (popmax 0.0123%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GFER p.Pro19Ser (c.55C>T)?

GFER p.Pro19Ser (c.55C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GFER p.Pro19Ser (c.55C>T) in the general population?

GFER p.Pro19Ser (c.55C>T) is ultra-rare (popmax 0.0123%, nfe) (gnomAD).

What do computational predictors say about GFER p.Pro19Ser (c.55C>T)?

AlphaMissense predicts likely benign (score 0.2142) — an in-silico prediction, not a clinical call.

GFER p.Pro19Ser

c.55C>T · rs893122483 · VCV2150355

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2142 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2142	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -6.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 1.07	unconstrained · MANE · 1,806 bp · p 0.23 · regional, not allelic
Overall
CADD	23.3	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

Grpmax group 0.0123% European (non-Finnish) · 138/1,122,154 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00996%

Overall 0.00953% 141/1,478,982 alleles · ultra-rare exomes 138/1,326,934 · genomes 3/152,048 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0123%	8,132
Admixed American	0.00237%	42,114
Remaining individualsnot grpmax-eligible	0.00175%	57,084
African / African-American	0.00147%	67,924

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.Pro19Ser
Coding: c.55C>T
MANE Select: NM_005262
dbSNP: rs893122483
Type: single nucleotide variant
Location: chr16:1984273 (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 19: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GFER p.Pro19= Benign ★★ same residue
GFER p.Pro19Leu Uncertain significance ★ ⚠ same residue
GFER p.Ser189Ter Pathogenic ★★ same condition
GFER p.Ala45Thr Uncertain significance ★★ ⚠ same condition
GFER p.Ala46Val Uncertain significance ★★ ⚠ same condition
GFER p.Ala73Ser Uncertain significance ★★ ⚠ same condition
GFER p.Asn14Lys Uncertain significance ★★ ⚠ same condition
GFER p.Asp43Glu Uncertain significance ★★ ⚠ 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/gfer-p-pro19ser (accessed [today's date]).

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