Is CHTF18 p.Ile489Val (c.1465A>G) pathogenic?

CHTF18 p.Ile489Val (c.1465A>G) is classified Uncertain significance in CHTF18 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.1571); Ultra-rare (popmax 0.023%, afr).

How common is CHTF18 p.Ile489Val (c.1465A>G) in the general population?

CHTF18 p.Ile489Val (c.1465A>G) is ultra-rare (popmax 0.023%, afr) (gnomAD).

What do computational predictors say about CHTF18 p.Ile489Val (c.1465A>G)?

AlphaMissense predicts likely benign (score 0.1571) — an in-silico prediction, not a clinical call.

CHTF18 p.Ile489Val

c.1465A>G · rs547838710 · VCV3144813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1571 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1571	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -9.05	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 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.43	unconstrained · MANE · 9,287 bp · p 1.1e-58 · regional, not allelic
Overall
CADD	24.0	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 0.023% African / African-American · 17/73,880 alleles

Filtering AF 0.0146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.012%

Overall 0.00182% 29/1,595,438 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.023%	4,346
Remaining individualsnot grpmax-eligible	0.0146%	6,857
Admixed American	0.00183%	54,566
South Asian	0.00112%	88,986
European (non-Finnish)	8.51e-05%	1,174,634

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.Ile489Val
Coding: c.1465A>G
MANE Select: NM_022092
dbSNP: rs547838710
Type: single nucleotide variant
Location: chr16:792577 (GRCh38)
Gene constraint: LOEUF 1.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.97 · 10 PDB
Residue 489: a β-strand

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-ile489val (accessed [today's date]).

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