Is RFT1 p.Ser428= (c.1284C>T) pathogenic?

RFT1 p.Ser428= (c.1284C>T) is classified Likely benign in RFT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-16). Very rare (popmax 0.00892%, eas); Associated with RFT1-congenital disorder of glycosylation.

What condition is associated with RFT1 p.Ser428= (c.1284C>T)?

RFT1 p.Ser428= (c.1284C>T) is associated with RFT1-congenital disorder of glycosylation (ClinVar).

How common is RFT1 p.Ser428= (c.1284C>T) in the general population?

RFT1 p.Ser428= (c.1284C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

How is RFT1-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

RFT1 p.Ser428=

c.1284C>T · rs773206764 · VCV1668770

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Conditions

RFT1-congenital disorder of glycosylation

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 -2.9	GERP -3.6
Overall
CADD	5.831	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,862 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00031% 5/1,612,480 alleles · very rare exomes 5/1,460,168 · genomes 0/152,312 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,216
European (non-Finnish)	8.48e-05%	1,179,553

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: RFT1
Protein: p.Ser428=
Coding: c.1284C>T
MANE Select: NM_052859
dbSNP: rs773206764
Type: single nucleotide variant
Location: chr3:53092543 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.46

Full RFT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

RFT1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For RFT1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

RFT1 p.Ser428Asn Uncertain significance ★★ same residue
RFT1 p.Arg442Gln Likely pathogenic ★★ same condition
RFT1 p.Arg67Cys Pathogenic/Likely pathogenic ★★ same condition
RFT1 p.Glu399Ter Likely pathogenic ★★ same condition
RFT1 p.Lys152Glu Pathogenic/Likely pathogenic ★★ same condition
RFT1 c.558+6A>T Uncertain significance ★★ same condition
RFT1 c.827-6T>G Uncertain significance ★★ same condition
RFT1 c.*184G>C 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/rft1-p-ser428 (accessed [today's date]).

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