Is CHD5 p.Asp424= (c.1272C>T) pathogenic?

CHD5 p.Asp424= (c.1272C>T) is classified Likely benign in CHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). Rare (popmax 0.552%, mid).

How common is CHD5 p.Asp424= (c.1272C>T) in the general population?

CHD5 p.Asp424= (c.1272C>T) is rare (popmax 0.552%, mid) (gnomAD).

CHD5 p.Asp424=

c.1272C>T · VCV4280784

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.552%, mid)

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 -0.42	GERP -4, phastCons 0.004
Overall
CADD	11.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.552% Middle Eastern · 27/4,892 alleles

Filtering AF 0.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.335%

Overall 0.058% 932/1,606,206 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.82%	122
Middle Easterngrpmax	0.552%	181
Remaining individualsnot grpmax-eligible	0.132%	757
South Asian	0.0786%	1,272
Admixed American	0.0606%	1,649
European (non-Finnish)	0.04%	2,498
African / African-American	0.00535%	18,699
Finnishnot grpmax-eligible	0.00157%	63,590

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: CHD5
Protein: p.Asp424=
Coding: c.1272C>T
MANE Select: NM_004627 · reported on NM_015557
Type: single nucleotide variant
Location: chr1:6148965 (GRCh38)
Structure: AlphaFold pLDDT 78.15 · 4 PDB

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

Similar variants

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CHD5 p.Pro1124Leu Pathogenic/Likely pathogenic ★★ same type
CHD5 p.Ser912Phe Pathogenic/Likely pathogenic ★★ same type
CHD5 c.2043+4A>T Uncertain significance ★★ same type
CHD5 c.79+5G>A Uncertain significance ★★ same type
CHD5 p.Ala1435Thr Uncertain significance ★★ ⚠ 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/chd5-p-asp424 (accessed [today's date]).

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