Is CHD3 p.Ser73Gly (c.217A>G) pathogenic?

CHD3 p.Ser73Gly (c.217A>G) is classified Likely benign in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). AlphaMissense: likely benign (0.1022); Ultra-rare (popmax 0.0119%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHD3 p.Ser73Gly (c.217A>G)?

CHD3 p.Ser73Gly (c.217A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHD3 p.Ser73Gly (c.217A>G) in the general population?

CHD3 p.Ser73Gly (c.217A>G) is ultra-rare (popmax 0.0119%, amr) (gnomAD).

What do computational predictors say about CHD3 p.Ser73Gly (c.217A>G)?

AlphaMissense predicts likely benign (score 0.1022) — an in-silico prediction, not a clinical call.

CHD3 p.Ser73Gly

c.217A>G · VCV4002109

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1022 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1022	likely benign
REVEL	0.519	indeterminate
SaProt	LLR -7.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.72	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,958 bp · p 0.95 · regional, not allelic
Overall
CADD	24.9	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

Grpmax group 0.0119% Admixed American · 6/50,482 alleles

Filtering AF 0.00516% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00349%

Overall 0.000822% 13/1,581,426 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0119%	8,414
African / African-American	0.00551%	18,147
Remaining individualsnot grpmax-eligible	0.00164%	60,976
South Asian	0.00115%	87,072
European (non-Finnish)	8.56e-05%	1,167,750

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHD3
Protein: p.Ser73Gly
Coding: c.217A>G
MANE Select: NM_001005273
Type: single nucleotide variant
Location: chr17:7890574 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 73: the 'disordered' region

Full CHD3 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

CHD3 p.Arg103Ter Pathogenic ★★ same condition
CHD3 p.Arg1078Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg966Trp Pathogenic ★★ same condition
CHD3 p.Arg985Trp Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Pro1918= Likely pathogenic ★★ same condition
CHD3 p.Arg1266Trp Uncertain significance ★★ ⚠ same condition
CHD3 p.Arg1377Cys Uncertain significance ★★ ⚠ same condition
CHD3 p.Arg1381Leu Uncertain significance ★★ ⚠ 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/chd3-p-ser73gly (accessed [today's date]).

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