Is CHD2 p.Ser958= (c.2874C>T) pathogenic?

CHD2 p.Ser958= (c.2874C>T) is classified Likely benign in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-10-05). Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with CHD2 p.Ser958= (c.2874C>T)?

CHD2 p.Ser958= (c.2874C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHD2 p.Ser958= (c.2874C>T) in the general population?

CHD2 p.Ser958= (c.2874C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

CHD2 p.Ser958=

c.2874C>T · rs1233633116 · VCV589936

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.43	GERP -1.3, phastCons 0.034
Overall
CADD	11.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,844 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,326 alleles · very rare exomes 4/1,461,288 · genomes 1/152,038 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,844
European (non-Finnish)	0.000339%	294,935

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: CHD2
Protein: p.Ser958=
Coding: c.2874C>T
MANE Select: NM_001271
dbSNP: rs1233633116
Type: single nucleotide variant
Location: chr15:92979281 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 958: a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance)

Full CHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD2 c.443+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Ala879Val Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Arg1152Trp Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Arg1637Ter Pathogenic ★★ same condition
CHD2 p.Arg1679Ter Pathogenic ★★ same condition
CHD2 p.Arg699Trp Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Arg804Ter Pathogenic ★★ same condition
CHD2 p.Thr645Met Pathogenic/Likely pathogenic ★★ 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/chd2-p-ser958 (accessed [today's date]).

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