Is CHD4 p.Arg80fs (c.238del) pathogenic?

CHD4 p.Arg80fs (c.238del) is classified Uncertain significance in CHD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-12).

CHD4 p.Arg80fs

c.238del · VCV3390497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 4 of 40
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CHD4
Protein: p.Arg80fs
Coding: c.238del
MANE Select: NM_001273
Type: Deletion
Location: chr12:6602160 (GRCh38)
Gene constraint: LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 65.41 · 12 PDB
Residue 80: the 'disordered' region

Full CHD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD4 p.Arg80Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CHD4 p.Lys354del Uncertain significance ★★ same type
CHD4 c.2514+8_2514+9del Likely benign ★★ same type
CHD4 c.3340+10_3340+12del Likely benign ★★ same type
CHD4 p.Leu1219fs Pathogenic ★ same type
CHD4 p.Val1298fs Likely pathogenic ★ same type
CHD4 p.Val888fs Likely pathogenic ★ same type
CHD4 c.4146_4147+10del 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/chd4-p-arg80fs (accessed [today's date]).

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