Is RFT1 p.Val141Phe (c.421G>T) pathogenic?

RFT1 p.Val141Phe (c.421G>T) is classified Uncertain significance in RFT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-07). AlphaMissense: ambiguous (0.3606); Absent from gnomAD v4.1; Associated with RFT1-congenital disorder of glycosylation.

What condition is associated with RFT1 p.Val141Phe (c.421G>T)?

RFT1 p.Val141Phe (c.421G>T) is associated with RFT1-congenital disorder of glycosylation (ClinVar).

How common is RFT1 p.Val141Phe (c.421G>T) in the general population?

RFT1 p.Val141Phe (c.421G>T) is absent from gnomAD v4.1 (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.Val141Phe (c.421G>T)?

AlphaMissense predicts ambiguous (score 0.3606) — an in-silico prediction, not a clinical call.

RFT1 p.Val141Phe

c.421G>T · rs2107164186 · VCV1519733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3606 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

RFT1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.3606	ambiguous
REVEL	0.671	pathogenic-leaning
SaProt	LLR -13.01	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP -2.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 38 kb · p 0.078 · regional, not allelic
Overall
CADD	22.9	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

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: RFT1
Protein: p.Val141Phe
Coding: c.421G>T
MANE Select: NM_052859
dbSNP: rs2107164186
Type: single nucleotide variant
Location: chr3:53122409 (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-val141phe (accessed [today's date]).

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