Is CHD3 p.Glu1303Asp (c.3909G>C) pathogenic?

CHD3 p.Glu1303Asp (c.3909G>C) is classified Uncertain significance in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-11). AlphaMissense: ambiguous (0.5422); Absent from gnomAD v4.1.

How common is CHD3 p.Glu1303Asp (c.3909G>C) in the general population?

CHD3 p.Glu1303Asp (c.3909G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD3 p.Glu1303Asp (c.3909G>C)?

AlphaMissense predicts ambiguous (score 0.5422) — an in-silico prediction, not a clinical call.

CHD3 p.Glu1303Asp

c.3909G>C · rs2151615191 · VCV1306197

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5422 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5422	ambiguous
REVEL	0.563	indeterminate
SaProt	LLR -7.42	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -1.8, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 3,550 bp · p 4.9e-38 · regional, not allelic
Overall
CADD	22.2	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: CHD3
Protein: p.Glu1303Asp
Coding: c.3909G>C
MANE Select: NM_001005273
dbSNP: rs2151615191
Type: single nucleotide variant
Location: chr17:7904456 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1303: a UniProt-annotated variant site (in snibcps)

Full CHD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD3 c.4073-2A>C Likely pathogenic ★★ same type
CHD3 p.Arg103Ter Pathogenic ★★ same type
CHD3 p.Arg1078Gln Pathogenic/Likely pathogenic ★★ same type
CHD3 p.Arg1121Pro Pathogenic/Likely pathogenic ★★ same type
CHD3 p.Arg1169Gln Pathogenic/Likely pathogenic ★★ same type
CHD3 p.Arg1169Pro Pathogenic/Likely pathogenic ★★ same type
CHD3 p.Arg1169Trp Pathogenic ★★ same type
CHD3 p.Arg1172Gln Pathogenic/Likely 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/chd3-p-glu1303asp (accessed [today's date]).

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