Is CHTF18 p.Ala790Val (c.2369C>T) pathogenic?

CHTF18 p.Ala790Val (c.2369C>T) is classified Uncertain significance in CHTF18 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.1195); Ultra-rare (popmax 0.0594%, nfe).

How common is CHTF18 p.Ala790Val (c.2369C>T) in the general population?

CHTF18 p.Ala790Val (c.2369C>T) is ultra-rare (popmax 0.0594%, nfe) (gnomAD).

What do computational predictors say about CHTF18 p.Ala790Val (c.2369C>T)?

AlphaMissense predicts likely benign (score 0.1195) — an in-silico prediction, not a clinical call.

CHTF18 p.Ala790Val

c.2369C>T · rs376802683 · VCV2371141

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1195 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0594%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1195	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -8.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.13, phastCons 1
Regional constraint	o/e 1.43	unconstrained · MANE · 9,287 bp · p 1.1e-58 · regional, not allelic
Overall
CADD	19.97	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0594% European (non-Finnish) · 700/1,178,168 alleles

Filtering AF 0.0558% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.0456% 733/1,608,728 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0594%	1,683
Remaining individualsnot grpmax-eligible	0.0385%	2,598
African / African-American	0.00801%	12,490
Admixed American	0.00504%	19,858

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.Ala790Val
Coding: c.2369C>T
MANE Select: NM_022092
dbSNP: rs376802683
Type: single nucleotide variant
Location: chr16:795990 (GRCh38)
Gene constraint: LOEUF 1.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.97 · 10 PDB
Residue 790: an α-helix

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

Similar variants

CHTF18 p.Ala790Thr Uncertain significance ★ ⚠ same residue
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

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-ala790val (accessed [today's date]).

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