Is CHTF8 p.Glu67Asp (c.201G>C) pathogenic?

CHTF8 p.Glu67Asp (c.201G>C) is classified Uncertain significance in CHTF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). AlphaMissense: likely benign (0.2055); Absent from gnomAD v4.1.

How common is CHTF8 p.Glu67Asp (c.201G>C) in the general population?

CHTF8 p.Glu67Asp (c.201G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHTF8 p.Glu67Asp (c.201G>C)?

AlphaMissense predicts likely benign (score 0.2055) — an in-silico prediction, not a clinical call.

CHTF8 p.Glu67Asp

c.201G>C · rs1961576802 · VCV3144854

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2055 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2055	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4	GERP 2.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,030 bp · p 0.29 · regional, not allelic
Overall
CADD	21.1	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: CHTF8
Protein: p.Glu67Asp
Coding: c.201G>C
MANE Select: NM_001039690
dbSNP: rs1961576802
Type: single nucleotide variant
Location: chr16:69120590 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 86.99

Full CHTF8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHTF8 p.Ala28Val Uncertain significance ★ ⚠ same type
CHTF8 p.Arg109Cys Uncertain significance ★ ⚠ same type
CHTF8 p.Arg29Cys Uncertain significance ★ ⚠ same type
CHTF8 p.Arg88His Uncertain significance ★ ⚠ same type
CHTF8 p.Arg88Ser Uncertain significance ★ ⚠ same type
CHTF8 p.Arg93Gln Uncertain significance ★ ⚠ same type
CHTF8 p.Arg93Trp Uncertain significance ★ ⚠ same type
CHTF8 p.Gly33Glu 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/chtf8-p-glu67asp (accessed [today's date]).

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