Is RTF2 p.Arg118Cys (c.352C>T) pathogenic?

RTF2 p.Arg118Cys (c.352C>T) is classified Uncertain significance in RTF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.1176); Ultra-rare (popmax 0.0134%, eas).

How common is RTF2 p.Arg118Cys (c.352C>T) in the general population?

RTF2 p.Arg118Cys (c.352C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about RTF2 p.Arg118Cys (c.352C>T)?

AlphaMissense predicts likely benign (score 0.1176) — an in-silico prediction, not a clinical call.

RTF2 p.Arg118Cys

c.352C>T · rs752235459 · VCV3156831

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1176 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1176	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -11.94	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 50 kb · p 0.00043 · regional, not allelic
Overall
CADD	26.3	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 0.0134% East Asian · 6/44,878 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00198% 32/1,613,888 alleles · ultra-rare exomes 29/1,461,686 · genomes 3/152,202 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,480
Remaining individualsnot grpmax-eligible	0.0064%	15,620
Admixed American	0.00333%	29,988
European (non-Finnish)	0.00161%	62,103
African / African-American	0.00134%	74,882

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: RTF2
Protein: p.Arg118Cys
Coding: c.352C>T
MANE Select: NM_016407
dbSNP: rs752235459
Type: single nucleotide variant
Location: chr20:56477078 (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.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
RTF2 p.Glu72Gln 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-arg118cys (accessed [today's date]).

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