Is RTF2 p.Asn173Ser (c.518A>G) pathogenic?

RTF2 p.Asn173Ser (c.518A>G) is classified Uncertain significance in RTF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-15). AlphaMissense: likely benign (0.2949); Ultra-rare (popmax 0.0133%, afr).

How common is RTF2 p.Asn173Ser (c.518A>G) in the general population?

RTF2 p.Asn173Ser (c.518A>G) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about RTF2 p.Asn173Ser (c.518A>G)?

AlphaMissense predicts likely benign (score 0.2949) — an in-silico prediction, not a clinical call.

RTF2 p.Asn173Ser

c.518A>G · rs140687107 · VCV3156838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2949 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, 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	0.2949	likely benign
REVEL	0.496	indeterminate
SaProt	LLR -11.55	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 50 kb · p 0.00043 · regional, not allelic
Overall
CADD	26.6	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 0.0133% African / African-American · 10/74,976 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00261% 42/1,608,792 alleles · ultra-rare exomes 29/1,456,546 · genomes 13/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,498
Admixed American	0.00845%	11,836
European (non-Finnish)	0.00221%	45,305
Remaining individualsnot grpmax-eligible	0.0016%	62,356

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.Asn173Ser
Coding: c.518A>G
MANE Select: NM_016407
dbSNP: rs140687107
Type: single nucleotide variant
Location: chr20:56513355 (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-asn173ser (accessed [today's date]).

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