Is CHD3 p.Pro240= (c.720C>T) pathogenic?

CHD3 p.Pro240= (c.720C>T) is classified Benign in CHD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-25). Rare (popmax 0.151%, eas); Associated with CHD3-related disorder.

What condition is associated with CHD3 p.Pro240= (c.720C>T)?

CHD3 p.Pro240= (c.720C>T) is associated with CHD3-related disorder (ClinVar).

How common is CHD3 p.Pro240= (c.720C>T) in the general population?

CHD3 p.Pro240= (c.720C>T) is rare (popmax 0.151%, eas) (gnomAD).

CHD3 p.Pro240=

c.720C>T · rs141834994 · VCV3042436

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.151%, eas)

Conditions

CHD3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.003	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.5
Overall
CADD	1.522	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.151% East Asian · 67/44,490 alleles

Filtering AF 0.122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.0326% 512/1,570,776 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.339%	295
East Asiangrpmax	0.151%	664
Admixed American	0.0556%	1,798
Remaining individualsnot grpmax-eligible	0.0509%	1,964
European (non-Finnish)	0.0229%	4,367
South Asian	0.0123%	8,163
African / African-American	0.0109%	9,200
Finnishnot grpmax-eligible	0.00158%	63,320

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro240=
Coding: c.720C>T
MANE Select: NM_001005273
dbSNP: rs141834994
Type: single nucleotide variant
Location: chr17:7893496 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 240: 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.Pro240His Uncertain significance ★ ⚠ same residue
CHD3 p.Pro240Thr Uncertain significance ★ ⚠ same residue
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

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-pro240 (accessed [today's date]).

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