Is CHTOP p.Arg169His (c.506G>A) pathogenic?

CHTOP p.Arg169His (c.506G>A) is classified Uncertain significance in CHTOP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: ambiguous (0.4681); Very rare (popmax 0.0017%, amr).

How common is CHTOP p.Arg169His (c.506G>A) in the general population?

CHTOP p.Arg169His (c.506G>A) is very rare (popmax 0.0017%, amr) (gnomAD).

What do computational predictors say about CHTOP p.Arg169His (c.506G>A)?

AlphaMissense predicts ambiguous (score 0.4681) — an in-silico prediction, not a clinical call.

CHTOP p.Arg169His

c.506G>A · rs1434663151 · VCV2470658

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Computational evidence

Protein change
AlphaMissense	0.4681	ambiguous
REVEL	0.487	indeterminate
SaProt	LLR -12.91	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,861 bp · p 0.37 · regional, not allelic
Overall
CADD	29.2	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 0.0017% Admixed American · 1/58,836 alleles

Filtering AF 0.000544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.00103% 15/1,455,360 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0017%	58,836
Remaining individualsnot grpmax-eligible	0.00161%	62,194
Finnishnot grpmax-eligible	0.00157%	63,750
European (non-Finnish)	0.00102%	98,092

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.Arg169His
Coding: c.506G>A
MANE Select: NM_015607
dbSNP: rs1434663151
Type: single nucleotide variant
Location: chr1:153643329 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.64
Residue 169: 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.Arg187Trp Uncertain significance ★ ⚠ same type
CHTOP p.Arg195Leu Uncertain significance ★ ⚠ same type
CHTOP p.Arg197Gln 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-arg169his (accessed [today's date]).

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