Is CHD5 p.Phe301= (c.903C>T) pathogenic?

CHD5 p.Phe301= (c.903C>T) is classified Benign in CHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). Common (popmax 71.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with parenti-mignot neurodevelopmental syndrome.

What condition is associated with CHD5 p.Phe301= (c.903C>T)?

CHD5 p.Phe301= (c.903C>T) is associated with parenti-mignot neurodevelopmental syndrome (ClinVar).

CHD5 p.Phe301=

Q: How common is CHD5 p.Phe301= (c.903C>T) in the general population?

CHD5 p.Phe301= (c.903C>T) is common (popmax 71.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.903C>T · rs9434711 · VCV2585660

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 71.8%, 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 -10	GERP -4
Overall
CADD	4.628	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 71.8% East Asian · 31,954/44,520 alleles

Filtering AF 71.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 70.8%

Overall 32.5% 522,294/1,606,776 alleles · common exomes 460,862/1,454,720 · genomes 61,432/152,056 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	71.8%	1
African / African-American	62.1%	2
South Asian	49.3%	2
Finnishnot grpmax-eligible	41.8%	2
Ashkenazi Jewishnot grpmax-eligible	34.8%	3
Remaining individualsnot grpmax-eligible	33.7%	3
Middle Eastern	32.9%	3
Amishnot grpmax-eligible	30.5%	3
European (non-Finnish)	27.7%	4
Admixed American	23.3%	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.Phe301=
Coding: c.903C>T
MANE Select: NM_015557
dbSNP: rs9434711
Type: single nucleotide variant
Location: chr1:6151123 (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 p.Phe301Ser Uncertain significance ★ ⚠ same residue
LCA5L p.Arg301Gln Uncertain significance ★ ⚠ same residue
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

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-phe301 (accessed [today's date]).

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