Is RTF1 p.Ile495Thr (c.1484T>C) pathogenic?

RTF1 p.Ile495Thr (c.1484T>C) is classified Uncertain significance in RTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely pathogenic (0.9887); Absent from gnomAD v4.1.

How common is RTF1 p.Ile495Thr (c.1484T>C) in the general population?

RTF1 p.Ile495Thr (c.1484T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RTF1 p.Ile495Thr (c.1484T>C)?

AlphaMissense predicts likely pathogenic (score 0.9887) — an in-silico prediction, not a clinical call.

RTF1 p.Ile495Thr

c.1484T>C · VCV3436075

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9887 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9887	likely pathogenic
REVEL	0.365	indeterminate
SaProt	LLR -12.96	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	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	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: RTF1
Protein: p.Ile495Thr
Coding: c.1484T>C
MANE Select: NM_015138
Type: single nucleotide variant
Location: chr15:41476447 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.15 · 18 PDB
Residue 495: 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.Arg501Lys 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-ile495thr (accessed [today's date]).

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