Is CPTP p.Arg110His (c.329G>A) pathogenic?

CPTP p.Arg110His (c.329G>A) is classified Uncertain significance in CPTP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). AlphaMissense: ambiguous (0.4225); Very rare (popmax 0.00906%, sas).

How common is CPTP p.Arg110His (c.329G>A) in the general population?

CPTP p.Arg110His (c.329G>A) is very rare (popmax 0.00906%, sas) (gnomAD).

What do computational predictors say about CPTP p.Arg110His (c.329G>A)?

AlphaMissense predicts ambiguous (score 0.4225) — an in-silico prediction, not a clinical call.

CPTP p.Arg110His

c.329G>A · VCV3496666

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4225 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00906%, sas)

Computational evidence

Protein change
AlphaMissense	0.4225	ambiguous
REVEL	0.491	indeterminate
SaProt	LLR -9.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 849 bp · p 0.1 · regional, not allelic
Overall
CADD	32.0	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 0.00906% South Asian · 8/88,284 alleles

Filtering AF 0.00449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00384%

Overall 0.00483% 76/1,575,122 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00906%	11,036
European (non-Finnish)	0.00531%	18,821
Remaining individualsnot grpmax-eligible	0.00489%	20,439
African / African-American	0.0027%	37,100
Admixed American	0.0018%	55,516

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.Arg110His
Coding: c.329G>A
MANE Select: NM_001029885
Type: single nucleotide variant
Location: chr1:1327447 (GRCh38)
Gene constraint: LOEUF 1.748 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.93 · 6 PDB
Residue 110: an α-helix; a binding site

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

Similar variants

CPTP p.Arg110Cys Uncertain significance ★ ⚠ 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.Arg126Cys Uncertain significance ★ ⚠ same type
CPTP p.Arg133Cys Uncertain significance ★ ⚠ same type
CPTP p.Arg155His 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-arg110his (accessed [today's date]).

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