Is CHD2 p.Ser1012Arg (c.3036T>G) pathogenic?

CHD2 p.Ser1012Arg (c.3036T>G) is classified Uncertain significance in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-09). AlphaMissense: likely pathogenic (0.9369); Absent from gnomAD v4.1.

How common is CHD2 p.Ser1012Arg (c.3036T>G) in the general population?

CHD2 p.Ser1012Arg (c.3036T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD2 p.Ser1012Arg (c.3036T>G)?

AlphaMissense predicts likely pathogenic (score 0.9369) — an in-silico prediction, not a clinical call.

CHD2 p.Ser1012Arg

c.3036T>G · rs768946382 · VCV1305445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9369 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9369	likely pathogenic
REVEL	0.149	moderately benign-leaning
SaProt	LLR -8.69	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.46	GERP 1.6, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 6,370 bp · p 7.8e-14 · regional, not allelic
Overall
CADD	23.2	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.Ser1012Arg
Coding: c.3036T>G
MANE Select: NM_001271
dbSNP: rs768946382
Type: single nucleotide variant
Location: chr15:92981427 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1012: 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

Similar variants

CHD2 p.Ser1012= 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-ser1012arg (accessed [today's date]).

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