Is RTF1 p.Arg501Lys (c.1502G>A) pathogenic?

RTF1 p.Arg501Lys (c.1502G>A) is classified Uncertain significance in RTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: likely benign (0.2696); Ultra-rare (popmax 0.015%, amr).

How common is RTF1 p.Arg501Lys (c.1502G>A) in the general population?

RTF1 p.Arg501Lys (c.1502G>A) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about RTF1 p.Arg501Lys (c.1502G>A)?

AlphaMissense predicts likely benign (score 0.2696) — an in-silico prediction, not a clinical call.

RTF1 p.Arg501Lys

c.1502G>A · rs201667884 · VCV3156821

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2696 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2696	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -9.36	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 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 6,904 bp · p 3.7e-14 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/59,990 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00465% 75/1,613,592 alleles · ultra-rare exomes 71/1,461,430 · genomes 4/152,162 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.169%	592
Admixed Americangrpmax	0.015%	6,666
Remaining individualsnot grpmax-eligible	0.0048%	20,819
European (non-Finnish)	0.0011%	90,748

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: RTF1
Protein: p.Arg501Lys
Coding: c.1502G>A
MANE Select: NM_015138
dbSNP: rs201667884
Type: single nucleotide variant
Location: chr15:41476465 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.15 · 18 PDB
Residue 501: an α-helix

Full RTF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RTF1 p.Ala90Gly Uncertain significance ★ ⚠ same type
RTF1 p.Arg267Gln Uncertain significance ★ ⚠ same type
RTF1 p.Arg267Trp Uncertain significance ★ ⚠ same type
RTF1 p.Arg271Gln Uncertain significance ★ ⚠ same type
RTF1 p.Arg330Cys Uncertain significance ★ ⚠ same type
RTF1 p.Arg333Gln Uncertain significance ★ ⚠ same type
RTF1 p.Arg361Gln Uncertain significance ★ ⚠ same type
RTF1 p.Arg568Pro Uncertain significance ★ ⚠ same type

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/rtf1-p-arg501lys (accessed [today's date]).

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