Is CHD2 p.Arg1138Thr (c.3413G>C) pathogenic?

CHD2 p.Arg1138Thr (c.3413G>C) is classified Uncertain significance in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). AlphaMissense: likely pathogenic (0.9934); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHD2 p.Arg1138Thr (c.3413G>C)?

CHD2 p.Arg1138Thr (c.3413G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CHD2 p.Arg1138Thr (c.3413G>C) in the general population?

CHD2 p.Arg1138Thr (c.3413G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD2 p.Arg1138Thr (c.3413G>C)?

AlphaMissense predicts likely pathogenic (score 0.9934) — an in-silico prediction, not a clinical call.

CHD2 p.Arg1138Thr

c.3413G>C · VCV3832775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9934 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9934	likely pathogenic
REVEL	0.593	indeterminate
SaProt	LLR -12.52	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.96	donor loss · deltas
Pangolin	Δ0.85	loss · gain 0.63 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 0.16, phastCons 1
Regional constraint	o/e 0.23	constrained · MANE · 7,276 bp · p 4.1e-09 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: CHD2
Protein: p.Arg1138Thr
Coding: c.3413G>C
MANE Select: NM_001271
Type: single nucleotide variant
Location: chr15:92985673 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1138: a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD2 c.443+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Ala879Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
CHD2 p.Arg1152Trp Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Arg1637Ter Pathogenic ★★ same condition
CHD2 p.Arg1679Ter Pathogenic ★★ same condition
CHD2 p.Arg699Trp Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Arg804Ter Pathogenic ★★ same condition
CHD2 p.Thr645Met Pathogenic/Likely pathogenic ★★ same condition

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-arg1138thr (accessed [today's date]).

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