Is RTF2 p.Lys23Glu (c.67A>G) pathogenic?

RTF2 p.Lys23Glu (c.67A>G) is classified Uncertain significance in RTF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-23). AlphaMissense: ambiguous (0.4956); No allele count reported in gnomAD v4.1 (AN 1,578,702).

How common is RTF2 p.Lys23Glu (c.67A>G) in the general population?

RTF2 p.Lys23Glu (c.67A>G) is no allele count reported in gnomAD v4.1 (AN 1,578,702) (gnomAD).

What do computational predictors say about RTF2 p.Lys23Glu (c.67A>G)?

AlphaMissense predicts ambiguous (score 0.4956) — an in-silico prediction, not a clinical call.

RTF2 p.Lys23Glu

c.67A>G · rs2515982391 · VCV3156844

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4956 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,578,702)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4956	ambiguous
REVEL	0.224	benign-leaning
SaProt	LLR -12.17	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 50 kb · p 0.00043 · regional, not allelic
Overall
CADD	33.0	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

No allele count reported in gnomAD v4.1 (AN 1,578,702). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RTF2
Protein: p.Lys23Glu
Coding: c.67A>G
MANE Select: NM_016407
dbSNP: rs2515982391
Type: single nucleotide variant
Location: chr20:56468764 (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-lys23glu (accessed [today's date]).

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