Is CHD3 p.Arg1650Ser (c.4950G>C) pathogenic?

CHD3 p.Arg1650Ser (c.4950G>C) is classified Likely benign in CHD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.2176); Ultra-rare (popmax 0.086%, sas); Associated with Inborn genetic diseases.

What condition is associated with CHD3 p.Arg1650Ser (c.4950G>C)?

CHD3 p.Arg1650Ser (c.4950G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CHD3 p.Arg1650Ser (c.4950G>C) in the general population?

CHD3 p.Arg1650Ser (c.4950G>C) is ultra-rare (popmax 0.086%, sas) (gnomAD).

What do computational predictors say about CHD3 p.Arg1650Ser (c.4950G>C)?

AlphaMissense predicts likely benign (score 0.2176) — an in-silico prediction, not a clinical call.

CHD3 p.Arg1650Ser

c.4950G>C · rs375492899 · VCV2379210

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2176 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.086%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2176	likely benign
REVEL	0.254	benign-leaning
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.87, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 1,113 bp · p 0.44 · regional, not allelic
Overall
CADD	16.23	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 0.086% South Asian · 67/77,862 alleles

Filtering AF 0.0695% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0635%

Overall 0.0106% 162/1,523,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.086%	1,162
Middle Eastern	0.035%	2,859
East Asian	0.0325%	3,080
African / African-American	0.0112%	8,965
Remaining individualsnot grpmax-eligible	0.0102%	9,788
Finnishnot grpmax-eligible	0.00649%	15,409
European (non-Finnish)	0.00526%	19,006
Admixed American	0.00258%	38,700

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.Arg1650Ser
Coding: c.4950G>C
MANE Select: NM_001005273
dbSNP: rs375492899
Type: single nucleotide variant
Location: chr17:7907626 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1650: the 'disordered' region; the 'required for interaction with pcnt' region; a UniProt-annotated variant site (in snibcps)

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.Arg1650Thr Likely benign ★ same residue
CHD3 p.Arg1650Gly Uncertain significance ★ ⚠ same residue
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

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-arg1650ser (accessed [today's date]).

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