Is CHTF18 p.Asp129Ala (c.386A>C) pathogenic?

CHTF18 p.Asp129Ala (c.386A>C) is classified Uncertain significance in CHTF18 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.0895); Absent from gnomAD v4.1.

How common is CHTF18 p.Asp129Ala (c.386A>C) in the general population?

CHTF18 p.Asp129Ala (c.386A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHTF18 p.Asp129Ala (c.386A>C)?

AlphaMissense predicts likely benign (score 0.0895) — an in-silico prediction, not a clinical call.

CHTF18 p.Asp129Ala

c.386A>C · rs2544311384 · VCV3144842

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0895 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0895	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -5.48	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 0.11	GERP -1.3, phastCons 0.018
Regional constraint	o/e 1.43	unconstrained · MANE · 9,287 bp · p 1.1e-58 · regional, not allelic
Overall
CADD	13.95	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHTF18
Protein: p.Asp129Ala
Coding: c.386A>C
MANE Select: NM_022092
dbSNP: rs2544311384
Type: single nucleotide variant
Location: chr16:789309 (GRCh38)
Gene constraint: LOEUF 1.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.97 · 10 PDB
Residue 129: the 'disordered' region

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-asp129ala (accessed [today's date]).

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