Is CHD5 p.Val368= (c.1104A>G) pathogenic?

CHD5 p.Val368= (c.1104A>G) is classified Benign in CHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). Common (popmax 71.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with parenti-mignot neurodevelopmental syndrome.

What condition is associated with CHD5 p.Val368= (c.1104A>G)?

CHD5 p.Val368= (c.1104A>G) is associated with parenti-mignot neurodevelopmental syndrome (ClinVar).

CHD5 p.Val368=

Q: How common is CHD5 p.Val368= (c.1104A>G) in the general population?

CHD5 p.Val368= (c.1104A>G) is common (popmax 71.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1104A>G · rs12565328 · VCV2585659

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 71.9%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

parenti-mignot neurodevelopmental syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -1.6, phastCons 0.9
Overall
CADD	6.982	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 71.9% East Asian · 32,140/44,694 alleles

Filtering AF 71.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 71%

Overall 33.3% 535,878/1,610,258 alleles · common exomes 473,556/1,460,434 · genomes 62,322/149,824 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	71.9%	1
African / African-American	65.6%	2
South Asian	52.5%	2
Finnishnot grpmax-eligible	42%	2
Ashkenazi Jewishnot grpmax-eligible	34.9%	3
Remaining individualsnot grpmax-eligible	34.8%	3
Middle Eastern	34.7%	3
Amishnot grpmax-eligible	30.5%	3
European (non-Finnish)	28.2%	4
Admixed American	24%	4

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: CHD5
Protein: p.Val368=
Coding: c.1104A>G
MANE Select: NM_015557
dbSNP: rs12565328
Type: single nucleotide variant
Location: chr1:6149303 (GRCh38)
Structure: AlphaFold pLDDT 78.15 · 4 PDB

Full CHD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

parenti-mignot neurodevelopmental syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD5 c.4171+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD5 p.Arg193Trp Pathogenic/Likely pathogenic ★★ same condition
CHD5 c.79+5G>A Uncertain significance ★★ same condition
CHD5 p.Ala215Val Uncertain significance ★★ same condition
CHD5 p.Asp23Asn Uncertain significance ★★ ⚠ same condition
CHD5 p.Lys818Arg Uncertain significance ★★ ⚠ same condition
CHD5 p.Pro1215Leu Uncertain significance ★★ ⚠ same condition
CHD5 p.Pro1409Ser 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/chd5-p-val368 (accessed [today's date]).

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