Is CPTP p.Arg196Cys (c.586C>T) pathogenic?

CPTP p.Arg196Cys (c.586C>T) is classified Uncertain significance in CPTP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: likely benign (0.1143); Rare (popmax 0.103%, amr).

How common is CPTP p.Arg196Cys (c.586C>T) in the general population?

CPTP p.Arg196Cys (c.586C>T) is rare (popmax 0.103%, amr) (gnomAD).

What do computational predictors say about CPTP p.Arg196Cys (c.586C>T)?

AlphaMissense predicts likely benign (score 0.1143) — an in-silico prediction, not a clinical call.

CPTP p.Arg196Cys

c.586C>T · VCV4233620

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1143 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1143	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -8.88	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 3.3	GERP -0.35, phastCons 0.31
Regional constraint	o/e 1.09	unconstrained · MANE · 849 bp · p 0.1 · regional, not allelic
Overall
CADD	20.8	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 0.103% Admixed American · 62/59,998 alleles

Filtering AF 0.0827% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0752%

Overall 0.00496% 80/1,612,662 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.103%	968
African / African-American	0.0173%	5,766
Remaining individualsnot grpmax-eligible	0.0032%	31,233
European (non-Finnish)	0.000254%	393,311

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: CPTP
Protein: p.Arg196Cys
Coding: c.586C>T
MANE Select: NM_001029885
Type: single nucleotide variant
Location: chr1:1327704 (GRCh38)
Gene constraint: LOEUF 1.748 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.93 · 6 PDB
Residue 196: an α-helix

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

Similar variants

CPTP p.Arg196His Likely benign ★ same residue
CPTP p.Ala132Thr Uncertain significance ★ ⚠ same type
CPTP p.Arg106Gln Uncertain significance ★ same type
CPTP p.Arg106Gly Uncertain significance ★ ⚠ same type
CPTP p.Arg106Trp Uncertain significance ★ ⚠ same type
CPTP p.Arg110Cys Uncertain significance ★ same type
CPTP p.Arg110His Uncertain significance ★ same type
CPTP p.Arg126Cys 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/cptp-p-arg196cys (accessed [today's date]).

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