Is CHD1 p.Arg618Ter (c.1852C>T) pathogenic?

CHD1 p.Arg618Ter (c.1852C>T) is classified Uncertain significance in CHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-17). Very rare (popmax 8.49e-05%, nfe).

How common is CHD1 p.Arg618Ter (c.1852C>T) in the general population?

CHD1 p.Arg618Ter (c.1852C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

CHD1 p.Arg618Ter

c.1852C>T · VCV4971575

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 14 of 36
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.2, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,592 alleles

Overall 6.21e-05% 1/1,609,064 alleles · very rare exomes 1/1,457,022 · genomes 0/152,042 · joint denominator

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: CHD1
Protein: p.Arg618Ter
Coding: c.1852C>T
MANE Select: NM_001270
Type: single nucleotide variant
Location: chr5:98893555 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.63 · 18 PDB
Residue 618: an α-helix; the helicase atp-binding domain; a UniProt-annotated variant site (in pilbos; patient cells show a global increase of methylated histone binding)

Full CHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD1 p.Arg618Gln Pathogenic same residue
CHD1 p.Arg1378Gly Uncertain significance ★★ ⚠ same type
CHD1 p.Arg1659Thr Uncertain significance ★★ ⚠ same type
CHD1 p.Arg1676Gly Uncertain significance ★★ ⚠ same type
CHD1 p.Arg1708Gln Uncertain significance ★★ same type
CHD1 p.Arg1708Trp Uncertain significance ★★ ⚠ same type
CHD1 p.Arg233His Uncertain significance ★★ same type
CHD1 p.Arg70Ter 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/chd1-p-arg618ter (accessed [today's date]).

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