Is QPCTL p.Arg287Cys (c.859C>T) pathogenic?

QPCTL p.Arg287Cys (c.859C>T) is classified Uncertain significance in QPCTL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely benign (0.1324); Rare (popmax 0.13%, nfe).

How common is QPCTL p.Arg287Cys (c.859C>T) in the general population?

QPCTL p.Arg287Cys (c.859C>T) is rare (popmax 0.13%, nfe) (gnomAD).

What do computational predictors say about QPCTL p.Arg287Cys (c.859C>T)?

AlphaMissense predicts likely benign (score 0.1324) — an in-silico prediction, not a clinical call.

QPCTL p.Arg287Cys

c.859C>T · rs145016874 · VCV2404923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1324 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.13%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1324	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -11.18	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 10 kb · p 0.13 · regional, not allelic
Overall
CADD	29.6	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 0.13% European (non-Finnish) · 1,538/1,179,948 alleles

Filtering AF 0.125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.105% 1,700/1,613,990 alleles · rare exomes 1,575/1,461,818 · genomes 125/152,172 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.13%	767
Remaining individualsnot grpmax-eligible	0.102%	977
South Asian	0.0736%	1,359
Middle Eastern	0.0495%	2,021
African / African-American	0.0227%	4,411
Admixed American	0.0183%	5,455

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.Arg287Cys
Coding: c.859C>T
MANE Select: NM_017659
dbSNP: rs145016874
Type: single nucleotide variant
Location: chr19:45698873 (GRCh38)
Gene constraint: LOEUF 1.284 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.12 · 7 PDB
Residue 287: an α-helix

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

Similar variants

QPCTL p.Arg287His 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
QPCTL p.Ala377Asp 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-arg287cys (accessed [today's date]).

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