Is RTF2 p.Lys69Thr (c.206A>C) pathogenic?

RTF2 p.Lys69Thr (c.206A>C) is classified Uncertain significance in RTF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: ambiguous (0.4238); Absent from gnomAD v4.1.

How common is RTF2 p.Lys69Thr (c.206A>C) in the general population?

RTF2 p.Lys69Thr (c.206A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RTF2 p.Lys69Thr (c.206A>C)?

AlphaMissense predicts ambiguous (score 0.4238) — an in-silico prediction, not a clinical call.

RTF2 p.Lys69Thr

c.206A>C · rs770430701 · VCV2542628

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4238 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4238	ambiguous
REVEL	0.269	benign-leaning
SaProt	LLR -8.47	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 50 kb · p 0.00043 · regional, not allelic
Overall
CADD	25.0	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

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.Lys69Thr
Coding: c.206A>C
MANE Select: NM_016407
dbSNP: rs770430701
Type: single nucleotide variant
Location: chr20:56474719 (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.Lys69Glu Uncertain significance ★ same residue
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

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-lys69thr (accessed [today's date]).

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