Is CHD2 p.Trp671Arg (c.2011T>C) pathogenic?

CHD2 p.Trp671Arg (c.2011T>C) is classified Uncertain significance in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: likely pathogenic (0.9971); Absent from gnomAD v4.1.

How common is CHD2 p.Trp671Arg (c.2011T>C) in the general population?

CHD2 p.Trp671Arg (c.2011T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD2 p.Trp671Arg (c.2011T>C)?

AlphaMissense predicts likely pathogenic (score 0.9971) — an in-silico prediction, not a clinical call.

CHD2 p.Trp671Arg

c.2011T>C · rs2505515661 · VCV1879309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9971 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9971	likely pathogenic · top 8% in CHD2
REVEL	0.731	pathogenic-leaning
SaProt	LLR -14.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.9, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 18 kb · p 1e-19 · regional, not allelic
Overall
CADD	25.0	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.Trp671Arg
Coding: c.2011T>C
MANE Select: NM_001271
dbSNP: rs2505515661
Type: single nucleotide variant
Location: chr15:92967335 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 671: 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.Trp671Ter Pathogenic ★ 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-trp671arg (accessed [today's date]).

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