Is CHD4 p.Ser337= (c.1011C>T) pathogenic?

CHD4 p.Ser337= (c.1011C>T) is classified Likely benign in CHD4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-18). Very rare (popmax 0.00401%, afr); Associated with CHD4-related disorder.

What condition is associated with CHD4 p.Ser337= (c.1011C>T)?

CHD4 p.Ser337= (c.1011C>T) is associated with CHD4-related disorder (ClinVar).

How common is CHD4 p.Ser337= (c.1011C>T) in the general population?

CHD4 p.Ser337= (c.1011C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

CHD4 p.Ser337=

c.1011C>T · VCV3347484

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

CHD4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.97	GERP 1.7, phastCons 1
Overall
CADD	8.834	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,872 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00197% 3/152,072 alleles · very rare

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: CHD4
Protein: p.Ser337=
Coding: c.1011C>T
MANE Select: NM_001273
Type: single nucleotide variant
Location: chr12:6600586 (GRCh38)
Gene constraint: LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 65.41 · 12 PDB
Residue 337: the 'disordered' region

Full CHD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CHD4-related disorder

Similar variants

CHD4 p.Glu536Val Uncertain significance ★★ ⚠ same condition
CHD4 p.Thr709Ala Uncertain significance ★★ ⚠ same condition
CHD4 p.Arg1068Ser Likely pathogenic ★ same condition
CHD4 p.Arg877Gln Likely pathogenic ★ same condition
CHD4 p.Cys376Ter Likely pathogenic ★ same condition
CHD4 p.Met1210Thr Likely pathogenic ★ ⚠ same condition
CHD4 p.Ala1601Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
CHD4 p.Arg1899Gly 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/chd4-p-ser337 (accessed [today's date]).

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