Is CHD3 p.Pro239Ser (c.715C>T) pathogenic?

CHD3 p.Pro239Ser (c.715C>T) is classified Likely benign in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-01). AlphaMissense: likely benign (0.0654); Very rare (popmax 0.00474%, eas).

How common is CHD3 p.Pro239Ser (c.715C>T) in the general population?

CHD3 p.Pro239Ser (c.715C>T) is very rare (popmax 0.00474%, eas) (gnomAD).

What do computational predictors say about CHD3 p.Pro239Ser (c.715C>T)?

AlphaMissense predicts likely benign (score 0.0654) — an in-silico prediction, not a clinical call.

CHD3 p.Pro239Ser

c.715C>T · VCV4821736

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00474%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0654	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -6.72	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 0.8	GERP -1.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 829 bp · p 0.013 · regional, not allelic
Overall
CADD	18.04	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 0.00474% East Asian · 2/42,180 alleles

Filtering AF 0.000786% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000294%

Overall 0.000567% 8/1,411,382 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00474%	21,090
Remaining individualsnot grpmax-eligible	0.00181%	55,372
European (non-Finnish)	0.000493%	202,973

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.Pro239Ser
Coding: c.715C>T
MANE Select: NM_001005273
Type: single nucleotide variant
Location: chr17:7893491 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 239: the 'disordered' region

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-pro239ser (accessed [today's date]).

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