Is RTF1 p.Arg271Gln (c.812G>A) pathogenic?

RTF1 p.Arg271Gln (c.812G>A) is classified Uncertain significance in RTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely pathogenic (0.6796); Very rare (popmax 0.00299%, nfe).

How common is RTF1 p.Arg271Gln (c.812G>A) in the general population?

RTF1 p.Arg271Gln (c.812G>A) is very rare (popmax 0.00299%, nfe) (gnomAD).

What do computational predictors say about RTF1 p.Arg271Gln (c.812G>A)?

AlphaMissense predicts likely pathogenic (score 0.6796) — an in-silico prediction, not a clinical call.

RTF1 p.Arg271Gln

c.812G>A · rs139619519 · VCV2598185

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00299%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6796	likely pathogenic
REVEL	0.225	benign-leaning
SaProt	LLR -9.70	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,366 bp · p 0.46 · regional, not allelic
Overall
CADD	25.2	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 0.00299% European (non-Finnish) · 35/1,170,026 alleles

Filtering AF 0.00217% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00192%

Overall 0.00226% 36/1,591,734 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00299%	33,429
Remaining individualsnot grpmax-eligible	0.00162%	61,606

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.Arg271Gln
Coding: c.812G>A
MANE Select: NM_015138
dbSNP: rs139619519
Type: single nucleotide variant
Location: chr15:41466175 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.15 · 18 PDB
Residue 271: an α-helix; the 'disordered' region

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.Arg330Cys Uncertain significance ★ ⚠ same type
RTF1 p.Arg333Gln Uncertain significance ★ ⚠ same type
RTF1 p.Arg361Gln Uncertain significance ★ ⚠ same type
RTF1 p.Arg501Lys 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-arg271gln (accessed [today's date]).

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