Is CHD8 p.Ser242= (c.726C>T) pathogenic?

CHD8 p.Ser242= (c.726C>T) is classified Likely benign in CHD8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-25). Very rare (popmax 0.00267%, afr).

How common is CHD8 p.Ser242= (c.726C>T) in the general population?

CHD8 p.Ser242= (c.726C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

CHD8 p.Ser242=

c.726C>T · rs906914158 · VCV2993684

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 9.9	GERP 2.9, phastCons 1
Overall
CADD	13.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,952 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000375% 6/1,599,342 alleles · very rare exomes 3/1,447,080 · genomes 3/152,262 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,476
South Asian	0.0011%	91,066
European (non-Finnish)	0.000254%	393,250

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: CHD8
Protein: p.Ser242=
Coding: c.726C>T
MANE Select: NM_001170629
dbSNP: rs906914158
Type: single nucleotide variant
Location: chr14:21430918 (GRCh38)
Gene constraint: LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.17 · 2 PDB

Full CHD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD8 p.Ser242Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
CHD8 p.Ser242Gly Uncertain significance ★ ⚠ same residue
CHD8 c.3882+1G>A Pathogenic/Likely pathogenic ★★ same type
CHD8 p.Arg1188Ter Pathogenic ★★ same type
CHD8 p.Arg1242Gln Likely pathogenic ★★ same type
CHD8 p.Arg1242Ter Pathogenic ★★ same type
CHD8 p.Arg1245Ter Pathogenic ★★ same type
CHD8 p.Arg1337Ter Pathogenic ★★ 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/chd8-p-ser242 (accessed [today's date]).

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