Is CHD3 p.Ser1219Ala (c.3655T>G) pathogenic?

CHD3 p.Ser1219Ala (c.3655T>G) is classified Uncertain significance in CHD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-14). AlphaMissense: likely benign (0.2999); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHD3 p.Ser1219Ala (c.3655T>G)?

CHD3 p.Ser1219Ala (c.3655T>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHD3 p.Ser1219Ala (c.3655T>G) in the general population?

CHD3 p.Ser1219Ala (c.3655T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD3 p.Ser1219Ala (c.3655T>G)?

AlphaMissense predicts likely benign (score 0.2999) — an in-silico prediction, not a clinical call.

CHD3 p.Ser1219Ala

c.3655T>G · rs2151604360 · VCV1334549

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2999	likely benign
REVEL	0.524	indeterminate
SaProt	LLR -6.93	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 3,550 bp · p 4.9e-38 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHD3
Protein: p.Ser1219Ala
Coding: c.3655T>G
MANE Select: NM_001005273
dbSNP: rs2151604360
Type: single nucleotide variant
Location: chr17:7903431 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1219: a modified residue (phosphoserine); the helicase c-terminal domain; a UniProt-annotated variant site (in snibcps)

Full CHD3 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

CHD3 p.Arg103Ter Pathogenic ★★ same condition
CHD3 p.Arg1078Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg966Trp Pathogenic ★★ same condition
CHD3 p.Arg985Trp Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Pro1918= Likely pathogenic ★★ same condition
CHD3 p.Arg1266Trp Uncertain significance ★★ ⚠ same condition
CHD3 p.Arg1377Cys Uncertain significance ★★ ⚠ same condition
CHD3 p.Arg1381Leu 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/chd3-p-ser1219ala (accessed [today's date]).

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