Is RFT1 p.Leu26Val (c.76T>G) pathogenic?

RFT1 p.Leu26Val (c.76T>G) is classified Likely benign in RFT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely benign (0.061); Ultra-rare (popmax 0.0847%, eas); Associated with Inborn genetic diseases.

What condition is associated with RFT1 p.Leu26Val (c.76T>G)?

RFT1 p.Leu26Val (c.76T>G) is associated with Inborn genetic diseases (ClinVar).

How common is RFT1 p.Leu26Val (c.76T>G) in the general population?

RFT1 p.Leu26Val (c.76T>G) is ultra-rare (popmax 0.0847%, eas) (gnomAD).

What do computational predictors say about RFT1 p.Leu26Val (c.76T>G)?

AlphaMissense predicts likely benign (score 0.061) — an in-silico prediction, not a clinical call.

RFT1 p.Leu26Val

c.76T>G · rs199628095 · VCV2592527

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.061 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0847%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.061	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.87	GERP -4.2, phastCons 0.017
Regional constraint	o/e 0.93	unconstrained · MANE · 38 kb · p 0.078 · regional, not allelic
Overall
CADD	4.827	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 0.0847% East Asian · 38/44,880 alleles

Filtering AF 0.0634% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.056%

Overall 0.00242% 39/1,613,254 alleles · ultra-rare exomes 34/1,460,874 · genomes 5/152,380 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0847%	1,181
Remaining individualsnot grpmax-eligible	0.0016%	62,468

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.Leu26Val
Coding: c.76T>G
MANE Select: NM_052859
dbSNP: rs199628095
Type: single nucleotide variant
Location: chr3:53125982 (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

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

Similar variants

RFT1 p.Ala323Gly Uncertain significance ★★ ⚠ same condition
RFT1 p.Ala395Thr Uncertain significance ★★ ⚠ same condition
RFT1 p.Ala463Val Uncertain significance ★★ ⚠ same condition
RFT1 p.Arg25Gln Uncertain significance ★★ ⚠ same condition
RFT1 p.Arg25Leu Uncertain significance ★★ ⚠ same condition
RFT1 p.Arg37Cys Uncertain significance ★★ ⚠ same condition
RFT1 p.Arg37His Uncertain significance ★★ ⚠ same condition
RFT1 p.Arg424Cys 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-leu26val (accessed [today's date]).

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