Is RTF2 p.Val181Met (c.541G>A) pathogenic?

RTF2 p.Val181Met (c.541G>A) is classified Uncertain significance in RTF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-15). AlphaMissense: likely benign (0.0648); Ultra-rare (popmax 0.0659%, mid).

How common is RTF2 p.Val181Met (c.541G>A) in the general population?

RTF2 p.Val181Met (c.541G>A) is ultra-rare (popmax 0.0659%, mid) (gnomAD).

What do computational predictors say about RTF2 p.Val181Met (c.541G>A)?

AlphaMissense predicts likely benign (score 0.0648) — an in-silico prediction, not a clinical call.

RTF2 p.Val181Met

c.541G>A · rs758627888 · VCV3156839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0648 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0659%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ 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	0.0648	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.6	GERP -5
Regional constraint	o/e 0.82	unconstrained · MANE · 50 kb · p 0.00043 · regional, not allelic
Overall
CADD	0.078	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0659% Middle Eastern · 4/6,070 alleles

Filtering AF 0.0375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0335%

Overall 0.00472% 76/1,608,820 alleles · ultra-rare exomes 72/1,456,688 · genomes 4/152,132 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0659%	1,517
South Asian	0.0491%	2,035
Remaining individualsnot grpmax-eligible	0.00642%	15,584
European (non-Finnish)	0.00187%	53,547
Admixed American	0.00169%	59,168
Finnishnot grpmax-eligible	0.00157%	63,684

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.Val181Met
Coding: c.541G>A
MANE Select: NM_016407
dbSNP: rs758627888
Type: single nucleotide variant
Location: chr20:56513378 (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-val181met (accessed [today's date]).

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