Is CHD2 p.Arg1052Thr (c.3155G>C) pathogenic?

CHD2 p.Arg1052Thr (c.3155G>C) is classified Likely pathogenic in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-21). AlphaMissense: likely pathogenic (0.9892); Absent from gnomAD v4.1.

How common is CHD2 p.Arg1052Thr (c.3155G>C) in the general population?

CHD2 p.Arg1052Thr (c.3155G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD2 p.Arg1052Thr (c.3155G>C)?

AlphaMissense predicts likely pathogenic (score 0.9892) — an in-silico prediction, not a clinical call.

CHD2 p.Arg1052Thr

c.3155G>C · rs2141850628 · VCV1313459

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9892 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9892	likely pathogenic ✓ concordant with ClinVar
REVEL	0.274	benign-leaning
SaProt	LLR -11.48	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 6,370 bp · p 7.8e-14 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

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: CHD2
Protein: p.Arg1052Thr
Coding: c.3155G>C
MANE Select: NM_001271
dbSNP: rs2141850628
Type: single nucleotide variant
Location: chr15:92984418 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1052: a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance); the 'disordered' region

Full CHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD2 p.Arg1052= Likely benign ★ same residue
CHD2 c.1153+1G>C Pathogenic ★★ same type
CHD2 c.1809+1G>A Pathogenic/Likely pathogenic ★★ same type
CHD2 c.294+1G>T Likely pathogenic ★★ same type
CHD2 c.443+1G>A Pathogenic/Likely pathogenic ★★ same type
CHD2 c.693-1G>A Likely pathogenic ★★ same type
CHD2 p.Ala879Val Pathogenic/Likely pathogenic ★★ ⚠ same type
CHD2 p.Arg1072Ter Pathogenic ★★ 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/chd2-p-arg1052thr (accessed [today's date]).

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