Is CPTP p.Ala136Thr (c.406G>A) pathogenic?

CPTP p.Ala136Thr (c.406G>A) is classified Likely benign in CPTP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: likely benign (0.0618); Ultra-rare (popmax 0.033%, mid).

How common is CPTP p.Ala136Thr (c.406G>A) in the general population?

CPTP p.Ala136Thr (c.406G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CPTP p.Ala136Thr (c.406G>A)?

AlphaMissense predicts likely benign (score 0.0618) — an in-silico prediction, not a clinical call.

CPTP p.Ala136Thr

c.406G>A · VCV3836048

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0618 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0618	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -5.64	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 -0.4	GERP -4.8
Regional constraint	o/e 1.09	unconstrained · MANE · 849 bp · p 0.1 · regional, not allelic
Overall
CADD	0.904	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 0.033% Middle Eastern · 2/6,052 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00196% 31/1,580,578 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,026
African / African-American	0.00673%	14,862
Remaining individualsnot grpmax-eligible	0.00326%	30,665
Admixed American	0.0018%	55,480
Finnishnot grpmax-eligible	0.0018%	55,616
European (non-Finnish)	0.00163%	61,383
South Asian	0.00113%	88,378

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.Ala136Thr
Coding: c.406G>A
MANE Select: NM_001029885
Type: single nucleotide variant
Location: chr1:1327524 (GRCh38)
Gene constraint: LOEUF 1.748 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.93 · 6 PDB
Residue 136: 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-ala136thr (accessed [today's date]).

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