Is RFT1 p.Val44= (c.132T>C) pathogenic?

RFT1 p.Val44= (c.132T>C) is classified Likely benign in RFT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-29). Very rare (popmax 0.00267%, afr); Associated with RFT1-congenital disorder of glycosylation.

What condition is associated with RFT1 p.Val44= (c.132T>C)?

RFT1 p.Val44= (c.132T>C) is associated with RFT1-congenital disorder of glycosylation (ClinVar).

How common is RFT1 p.Val44= (c.132T>C) in the general population?

RFT1 p.Val44= (c.132T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

How is RFT1-CDG inherited?

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

RFT1 p.Val44=

c.132T>C · rs1218035102 · VCV1615165

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 1.6	GERP -4.2, phastCons 1
Overall
CADD	7.625	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,940 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,716 alleles · very rare exomes 1/1,461,470 · genomes 1/152,246 · 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.Val44=
Coding: c.132T>C
MANE Select: NM_052859
dbSNP: rs1218035102
Type: single nucleotide variant
Location: chr3:53125926 (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.Val44Ala 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-val44 (accessed [today's date]).

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