Is QPCTL p.Arg284Pro (c.851G>C) pathogenic?

QPCTL p.Arg284Pro (c.851G>C) is classified Uncertain significance in QPCTL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-17). AlphaMissense: likely benign (0.12); Ultra-rare (popmax 0.0174%, afr).

How common is QPCTL p.Arg284Pro (c.851G>C) in the general population?

QPCTL p.Arg284Pro (c.851G>C) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about QPCTL p.Arg284Pro (c.851G>C)?

AlphaMissense predicts likely benign (score 0.12) — an in-silico prediction, not a clinical call.

QPCTL p.Arg284Pro

c.851G>C · rs201435176 · VCV2537069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.12 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.12	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -5.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.96	GERP -1.8, phastCons 0.035
Regional constraint	o/e 0.93	unconstrained · MANE · 10 kb · p 0.13 · regional, not allelic
Overall
CADD	21.9	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 0.0174% African / African-American · 13/74,870 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.000868% 14/1,613,770 alleles · ultra-rare exomes 8/1,461,816 · genomes 6/151,954 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,759
Admixed American	0.00167%	59,968

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: QPCTL
Protein: p.Arg284Pro
Coding: c.851G>C
MANE Select: NM_017659
dbSNP: rs201435176
Type: single nucleotide variant
Location: chr19:45698865 (GRCh38)
Gene constraint: LOEUF 1.284 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.12 · 7 PDB
Residue 284: an α-helix

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

Similar variants

QPCTL p.Arg284Cys Uncertain significance ★ ⚠ same residue
QPCTL p.Arg284His Uncertain significance ★ ⚠ same residue
QPCTL p.Arg161His Benign ★★ same type
QPCTL p.Ala159Asp Uncertain significance ★ ⚠ same type
QPCTL p.Ala212Glu Uncertain significance ★ ⚠ same type
QPCTL p.Ala213Gly Uncertain significance ★ ⚠ same type
QPCTL p.Ala273Val Uncertain significance ★ ⚠ same type
QPCTL p.Ala354Val 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/qpctl-p-arg284pro (accessed [today's date]).

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