Is RTF2 p.Tyr304Cys (c.911A>G) pathogenic?

RTF2 p.Tyr304Cys (c.911A>G) is classified Uncertain significance in RTF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). AlphaMissense: likely pathogenic (0.6668); Very rare (popmax 0.00268%, afr).

How common is RTF2 p.Tyr304Cys (c.911A>G) in the general population?

RTF2 p.Tyr304Cys (c.911A>G) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about RTF2 p.Tyr304Cys (c.911A>G)?

AlphaMissense predicts likely pathogenic (score 0.6668) — an in-silico prediction, not a clinical call.

RTF2 p.Tyr304Cys

c.911A>G · VCV3948514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6668 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.6668	likely pathogenic
REVEL	0.55	indeterminate
SaProt	LLR -8.52	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 0.71, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 50 kb · p 0.00043 · regional, not allelic
Overall
CADD	27.1	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 0.00268% African / African-American · 2/74,734 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00031% 5/1,611,604 alleles · very rare exomes 3/1,459,438 · genomes 2/152,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,367
South Asian	0.0011%	90,708
European (non-Finnish)	0.00017%	589,637

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.Tyr304Cys
Coding: c.911A>G
MANE Select: NM_016407
Type: single nucleotide variant
Location: chr20:56518255 (GRCh38)

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

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-tyr304cys (accessed [today's date]).

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