Is CHTF18 p.Arg404Cys (c.1210C>T) pathogenic?

CHTF18 p.Arg404Cys (c.1210C>T) is classified Uncertain significance in CHTF18 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: ambiguous (0.5108); Rare (popmax 0.227%, eas).

How common is CHTF18 p.Arg404Cys (c.1210C>T) in the general population?

CHTF18 p.Arg404Cys (c.1210C>T) is rare (popmax 0.227%, eas) (gnomAD).

What do computational predictors say about CHTF18 p.Arg404Cys (c.1210C>T)?

AlphaMissense predicts ambiguous (score 0.5108) — an in-silico prediction, not a clinical call.

CHTF18 p.Arg404Cys

c.1210C>T · rs771696368 · VCV2367279

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5108 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.227%, eas)

Computational evidence

Protein change
AlphaMissense	0.5108	ambiguous
REVEL	0.527	indeterminate
SaProt	LLR -12.79	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.5, phastCons 1
Regional constraint	o/e 1.43	unconstrained · MANE · 9,287 bp · p 1.1e-58 · regional, not allelic
Overall
CADD	28.1	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 0.227% East Asian · 95/41,830 alleles

Filtering AF 0.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.176%

Overall 0.0229% 359/1,570,440 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.227%	440
Admixed American	0.0275%	3,639
European (non-Finnish)	0.0183%	5,466
African / African-American	0.0177%	5,662
Remaining individualsnot grpmax-eligible	0.0148%	6,757
South Asian	0.0106%	9,474
Ashkenazi Jewishnot grpmax-eligible	0.00694%	14,419
Finnishnot grpmax-eligible	0.0067%	14,919

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: CHTF18
Protein: p.Arg404Cys
Coding: c.1210C>T
MANE Select: NM_022092
dbSNP: rs771696368
Type: single nucleotide variant
Location: chr16:792231 (GRCh38)
Gene constraint: LOEUF 1.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.97 · 10 PDB

Full CHTF18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHTF18 p.Ala770= Benign ★★ same type
CHTF18 p.Arg804Cys Benign ★★ same type
CHTF18 p.Asn820= Benign ★★ same type
CHTF18 p.Asp284Glu Benign ★★ same type
CHTF18 p.Glu233Lys Benign ★★ same type
CHTF18 p.His179= Benign ★★ same type
CHTF18 p.Leu541= Benign ★★ same type
CHTF18 p.Leu797= Benign ★★ 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/chtf18-p-arg404cys (accessed [today's date]).

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