Is CHTOP p.Arg197Gln (c.590G>A) pathogenic?

CHTOP p.Arg197Gln (c.590G>A) is classified Uncertain significance in CHTOP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-26). AlphaMissense: ambiguous (0.4215); Very rare (popmax 0.00834%, amr).

How common is CHTOP p.Arg197Gln (c.590G>A) in the general population?

CHTOP p.Arg197Gln (c.590G>A) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about CHTOP p.Arg197Gln (c.590G>A)?

AlphaMissense predicts ambiguous (score 0.4215) — an in-silico prediction, not a clinical call.

CHTOP p.Arg197Gln

c.590G>A · rs141966064 · VCV3144859

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4215 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Computational evidence

Protein change
AlphaMissense	0.4215	ambiguous
REVEL	0.464	indeterminate
SaProt	LLR -12.38	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,861 bp · p 0.37 · regional, not allelic
Overall
CADD	25.7	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 0.00834% Admixed American · 5/59,976 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.0039% 63/1,613,712 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,995
African / African-American	0.00802%	12,472
South Asian	0.00439%	22,769
European (non-Finnish)	0.00398%	25,107
East Asian	0.00223%	44,884

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.Arg197Gln
Coding: c.590G>A
MANE Select: NM_015607
dbSNP: rs141966064
Type: single nucleotide variant
Location: chr1:153645112 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.64
Residue 197: the 'disordered' region; the 'interaction with prmt1' region

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-arg197gln (accessed [today's date]).

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