Is CHD3 p.Pro1939Ser (c.5815C>T) pathogenic?

CHD3 p.Pro1939Ser (c.5815C>T) is classified Likely benign in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.0903); Very rare (popmax 0.00746%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHD3 p.Pro1939Ser (c.5815C>T)?

CHD3 p.Pro1939Ser (c.5815C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHD3 p.Pro1939Ser (c.5815C>T) in the general population?

CHD3 p.Pro1939Ser (c.5815C>T) is very rare (popmax 0.00746%, nfe) (gnomAD).

What do computational predictors say about CHD3 p.Pro1939Ser (c.5815C>T)?

AlphaMissense predicts likely benign (score 0.0903) — an in-silico prediction, not a clinical call.

CHD3 p.Pro1939Ser

c.5815C>T · rs369604836 · VCV3144122

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00746%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0903	likely benign
REVEL	0.233	benign-leaning
SaProt	LLR -6.39	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 4	GERP 0.73, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 1,019 bp · p 0.084 · regional, not allelic
Overall
CADD	21.2	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

Grpmax group 0.00746% European (non-Finnish) · 88/1,179,854 alleles

Filtering AF 0.00615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00573%

Overall 0.00558% 90/1,613,518 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00746%	13,407
Remaining individualsnot grpmax-eligible	0.0016%	62,456
African / African-American	0.00134%	74,872

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.Pro1939Ser
Coding: c.5815C>T
MANE Select: NM_001005273
dbSNP: rs369604836
Type: single nucleotide variant
Location: chr17:7910907 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1939: 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.Pro1939Ala Uncertain significance ★ ⚠ same residue
CHD3 p.Pro1939= Likely benign ★ 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-pro1939ser (accessed [today's date]).

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