Is CHD2 p.Ser1407Thr (c.4219T>A) pathogenic?

CHD2 p.Ser1407Thr (c.4219T>A) is classified Benign/Likely benign in CHD2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0601); Low-frequency (popmax 3.09%, sas); Associated with Inborn genetic diseases.

What condition is associated with CHD2 p.Ser1407Thr (c.4219T>A)?

CHD2 p.Ser1407Thr (c.4219T>A) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Ser1407Thr (c.4219T>A) in the general population?

CHD2 p.Ser1407Thr (c.4219T>A) is low-frequency (popmax 3.09%, sas) (gnomAD).

What do computational predictors say about CHD2 p.Ser1407Thr (c.4219T>A)?

AlphaMissense predicts likely benign (score 0.0601) — an in-silico prediction, not a clinical call.

CHD2 p.Ser1407Thr

c.4219T>A · rs61756301 · VCV238881

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0601 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.09%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0601	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -7.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 6,067 bp · p 0.73 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.09% South Asian · 2,727/88,394 alleles

Filtering AF 2.99% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.95%

Overall 1.64% 26,240/1,600,670 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	3.09%	32
Middle Eastern	2.54%	39
Finnishnot grpmax-eligible	1.91%	52
European (non-Finnish)	1.72%	58
Remaining individualsnot grpmax-eligible	1.69%	59
Ashkenazi Jewishnot grpmax-eligible	1.12%	89
Admixed American	0.71%	141
African / African-American	0.268%	373
Amishnot grpmax-eligible	0.11%	912
East Asian	0.0135%	7,424

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.Ser1407Thr
Coding: c.4219T>A
MANE Select: NM_001271
dbSNP: rs61756301
Type: single nucleotide variant
Location: chr15:93002258 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1407: a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance); the 'disordered' region

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

Also linked: developmental and epileptic encephalopathy 94

Similar variants

CHD2 p.Ser1407Tyr Uncertain significance ★ ⚠ same residue
CHD2 p.Ser1407Ile Uncertain significance ★ same residue
CHD2 c.1153+1G>C Pathogenic ★★ same condition
CHD2 c.1809+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD2 c.294+1G>T Likely pathogenic ★★ same condition
CHD2 c.443+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD2 c.693-1G>A Likely pathogenic ★★ same condition
CHD2 p.Ala879Val 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-ser1407thr (accessed [today's date]).

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