Is CHTOP p.Pro113Arg (c.338C>G) pathogenic?

CHTOP p.Pro113Arg (c.338C>G) is classified Uncertain significance in CHTOP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-05). AlphaMissense: ambiguous (0.4898); Very rare (popmax 8.47e-05%, nfe).

How common is CHTOP p.Pro113Arg (c.338C>G) in the general population?

CHTOP p.Pro113Arg (c.338C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CHTOP p.Pro113Arg (c.338C>G)?

AlphaMissense predicts ambiguous (score 0.4898) — an in-silico prediction, not a clinical call.

CHTOP p.Pro113Arg

c.338C>G · VCV3492835

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4898 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4898	ambiguous
REVEL	0.342	indeterminate
SaProt	LLR -6.26	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,861 bp · p 0.37 · regional, not allelic
Overall
CADD	23.7	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 8.47e-05% European (non-Finnish) · 1/1,180,004 alleles

Overall 6.84e-05% 1/1,461,848 alleles · very rare

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: CHTOP
Protein: p.Pro113Arg
Coding: c.338C>G
MANE Select: NM_015607
Type: single nucleotide variant
Location: chr1:153642364 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.64

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

Similar variants

CHTOP p.Ala99Ser Uncertain significance ★ ⚠ same type
CHTOP p.Arg110Lys Uncertain significance ★ ⚠ same type
CHTOP p.Arg124Thr Uncertain significance ★ ⚠ same type
CHTOP p.Arg157Gln Uncertain significance ★ ⚠ same type
CHTOP p.Arg159His Uncertain significance ★ ⚠ same type
CHTOP p.Arg169His Uncertain significance ★ ⚠ same type
CHTOP p.Arg187Trp Uncertain significance ★ ⚠ same type
CHTOP p.Arg195Leu 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/chtop-p-pro113arg (accessed [today's date]).

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