Is QRFPR p.Arg16Pro (c.47G>C) pathogenic?

QRFPR p.Arg16Pro (c.47G>C) is classified Uncertain significance in QRFPR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: ambiguous (0.3968); Very rare (popmax 0.00537%, nfe).

How common is QRFPR p.Arg16Pro (c.47G>C) in the general population?

QRFPR p.Arg16Pro (c.47G>C) is very rare (popmax 0.00537%, nfe) (gnomAD).

What do computational predictors say about QRFPR p.Arg16Pro (c.47G>C)?

AlphaMissense predicts ambiguous (score 0.3968) — an in-silico prediction, not a clinical call.

QRFPR p.Arg16Pro

c.47G>C · rs768283361 · VCV3150332

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3968 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00537%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3968	ambiguous
REVEL	0.394	indeterminate
SaProt	LLR -13.68	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.47	GERP -0.24
Regional constraint	o/e 1.02	unconstrained · MANE · 51 kb · p 0.68 · regional, not allelic
Overall
CADD	22.5	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 0.00537% European (non-Finnish) · 63/1,173,018 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0039%

Overall 0.00406% 65/1,601,562 alleles · very rare exomes 59/1,449,344 · genomes 6/152,218 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00537%	18,619
Remaining individualsnot grpmax-eligible	0.00162%	61,776
South Asian	0.00111%	89,796

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: QRFPR
Protein: p.Arg16Pro
Coding: c.47G>C
MANE Select: NM_198179
dbSNP: rs768283361
Type: single nucleotide variant
Location: chr4:121380601 (GRCh38)
Gene constraint: LOEUF 1.532 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.74 · 2 PDB
Residue 16: an α-helix

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

Similar variants

QRFPR p.Ile296Thr Uncertain significance ★★ ⚠ same type
QRFPR p.Ala128Thr Uncertain significance ★ ⚠ same type
QRFPR p.Ala315Val Uncertain significance ★ ⚠ same type
QRFPR p.Arg13Trp Uncertain significance ★ ⚠ same type
QRFPR p.Arg160Gln Uncertain significance ★ ⚠ same type
QRFPR p.Arg161Thr Uncertain significance ★ ⚠ same type
QRFPR p.Arg22Gln Uncertain significance ★ ⚠ same type
QRFPR p.Asn110Asp 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/qrfpr-p-arg16pro (accessed [today's date]).

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