Is CHD3 p.Pro23Ser (c.67C>T) pathogenic?

CHD3 p.Pro23Ser (c.67C>T) is classified Likely benign in CHD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-26). AlphaMissense: likely benign (0.0774); Rare (popmax 0.277%, afr); Associated with CHD3-related disorder.

What condition is associated with CHD3 p.Pro23Ser (c.67C>T)?

CHD3 p.Pro23Ser (c.67C>T) is associated with CHD3-related disorder (ClinVar).

How common is CHD3 p.Pro23Ser (c.67C>T) in the general population?

CHD3 p.Pro23Ser (c.67C>T) is rare (popmax 0.277%, afr) (gnomAD).

What do computational predictors say about CHD3 p.Pro23Ser (c.67C>T)?

AlphaMissense predicts likely benign (score 0.0774) — an in-silico prediction, not a clinical call.

CHD3 p.Pro23Ser

c.67C>T · rs61740589 · VCV3050085

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0774 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.277%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CHD3-related disorder

Computational evidence

Protein change
AlphaMissense	0.0774	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -5.77	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 -0.15	GERP -0.94
Regional constraint	o/e 1.01	unconstrained · MANE · 1,958 bp · p 0.95 · regional, not allelic
Overall
CADD	13.05	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 0.277% African / African-American · 208/75,044 alleles

Filtering AF 0.246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.234%

Overall 0.0217% 351/1,614,234 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.277%	361
Remaining individualsnot grpmax-eligible	0.0736%	1,359
Admixed American	0.0233%	4,288
European (non-Finnish)	0.00695%	14,391
South Asian	0.0011%	91,092

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.Pro23Ser
Coding: c.67C>T
MANE Select: NM_001005273
dbSNP: rs61740589
Type: single nucleotide variant
Location: chr17:7889067 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 23: the 'disordered' region

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

Disease context

CHD3-related disorder

Similar variants

CHD3 p.Arg1172Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1342Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg985Gln Pathogenic ★★ same condition
CHD3 p.Arg1491His Uncertain significance ★★ ⚠ same condition
CHD3 p.Arg684Ter Pathogenic ★ same condition
CHD3 p.Glu1653Ter Likely pathogenic ★ same condition
CHD3 p.Met1085Ile Likely pathogenic ★ same condition
CHD3 p.Ala1289Thr Conflicting classifications of pathogenicity ★ ⚠ 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-pro23ser (accessed [today's date]).

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