Is RFT1 p.Ser207Cys (c.620C>G) pathogenic?

RFT1 p.Ser207Cys (c.620C>G) is classified Uncertain significance in RFT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-06). AlphaMissense: likely benign (0.0868); Very rare (popmax 8.48e-05%, nfe); Associated with RFT1-congenital disorder of glycosylation.

What condition is associated with RFT1 p.Ser207Cys (c.620C>G)?

RFT1 p.Ser207Cys (c.620C>G) is associated with RFT1-congenital disorder of glycosylation (ClinVar).

How common is RFT1 p.Ser207Cys (c.620C>G) in the general population?

RFT1 p.Ser207Cys (c.620C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is RFT1-CDG inherited?

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

What do computational predictors say about RFT1 p.Ser207Cys (c.620C>G)?

AlphaMissense predicts likely benign (score 0.0868) — an in-silico prediction, not a clinical call.

RFT1 p.Ser207Cys

c.620C>G · rs758629887 · VCV2107432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0868 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

RFT1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0868	likely benign
REVEL	0.667	pathogenic-leaning
SaProt	LLR -10.83	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 0.23, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 38 kb · p 0.078 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,174 alleles

Overall 6.2e-05% 1/1,612,288 alleles · very rare exomes 1/1,460,024 · genomes 0/152,264 · 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: RFT1
Protein: p.Ser207Cys
Coding: c.620C>G
MANE Select: NM_052859
dbSNP: rs758629887
Type: single nucleotide variant
Location: chr3:53119960 (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.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
RFT1 p.Ala233Val 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-ser207cys (accessed [today's date]).

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