Is CPTP p.Met82Ile (c.246G>T) pathogenic?

CPTP p.Met82Ile (c.246G>T) is classified Uncertain significance in CPTP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely pathogenic (0.9167); Very rare (popmax 0.00458%, nfe).

How common is CPTP p.Met82Ile (c.246G>T) in the general population?

CPTP p.Met82Ile (c.246G>T) is very rare (popmax 0.00458%, nfe) (gnomAD).

What do computational predictors say about CPTP p.Met82Ile (c.246G>T)?

AlphaMissense predicts likely pathogenic (score 0.9167) — an in-silico prediction, not a clinical call.

CPTP p.Met82Ile

c.246G>T · rs765913702 · VCV2515738

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9167 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9167	likely pathogenic · top 6% in CPTP
REVEL	0.43	indeterminate
SaProt	LLR -10.92	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 849 bp · p 0.1 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00458% European (non-Finnish) · 54/1,178,954 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.0035% 56/1,598,240 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00458%	21,832
Remaining individualsnot grpmax-eligible	0.00321%	31,150

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.Met82Ile
Coding: c.246G>T
MANE Select: NM_001029885
dbSNP: rs765913702
Type: single nucleotide variant
Location: chr1:1327364 (GRCh38)
Gene constraint: LOEUF 1.748 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.93 · 6 PDB
Residue 82: an α-helix

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

Similar variants

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
CPTP p.Arg133Cys 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-met82ile (accessed [today's date]).

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