Is RTF2 p.Leu67Val (c.199T>G) pathogenic?

RTF2 p.Leu67Val (c.199T>G) is classified Uncertain significance in RTF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely pathogenic (0.5907); Absent from gnomAD v4.1.

How common is RTF2 p.Leu67Val (c.199T>G) in the general population?

RTF2 p.Leu67Val (c.199T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RTF2 p.Leu67Val (c.199T>G)?

AlphaMissense predicts likely pathogenic (score 0.5907) — an in-silico prediction, not a clinical call.

RTF2 p.Leu67Val

c.199T>G · VCV3436080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5907 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5907	likely pathogenic
REVEL	0.437	indeterminate
SaProt	LLR -10.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.64	GERP -5.3
Regional constraint	o/e 0.82	unconstrained · MANE · 50 kb · p 0.00043 · regional, not allelic
Overall
CADD	17.21	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: RTF2
Protein: p.Leu67Val
Coding: c.199T>G
MANE Select: NM_016407
Type: single nucleotide variant
Location: chr20:56474712 (GRCh38)
Gene constraint: LOEUF 0.806 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.24

Full RTF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RTF2 p.Arg118Cys Uncertain significance ★ ⚠ same type
RTF2 p.Arg147Pro Uncertain significance ★ ⚠ same type
RTF2 p.Arg46Gln Uncertain significance ★ ⚠ same type
RTF2 p.Asn87Ser Uncertain significance ★ ⚠ same type
RTF2 p.Asn96Ser Uncertain significance ★ same type
RTF2 p.Asp25Asn Uncertain significance ★ same type
RTF2 p.Cys135Phe Uncertain significance ★ ⚠ same type
RTF2 p.Cys140Tyr 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/rtf2-p-leu67val (accessed [today's date]).

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