Is CHD3 p.Ser597Phe (c.1790C>T) pathogenic?

CHD3 p.Ser597Phe (c.1790C>T) is classified Uncertain significance in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). AlphaMissense: likely pathogenic (0.7984); Very rare (popmax 0.00102%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHD3 p.Ser597Phe (c.1790C>T)?

CHD3 p.Ser597Phe (c.1790C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHD3 p.Ser597Phe (c.1790C>T) in the general population?

CHD3 p.Ser597Phe (c.1790C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about CHD3 p.Ser597Phe (c.1790C>T)?

AlphaMissense predicts likely pathogenic (score 0.7984) — an in-silico prediction, not a clinical call.

CHD3 p.Ser597Phe

c.1790C>T · VCV3491964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7984 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7984	likely pathogenic
REVEL	0.541	indeterminate
SaProt	LLR -8.50	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 1,913 bp · p 8e-06 · regional, not allelic
Overall
CADD	28.0	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 0.00102% European (non-Finnish) · 12/1,180,028 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000743% 12/1,614,016 alleles · very rare exomes 10/1,461,874 · genomes 2/152,142 · joint denominator

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: CHD3
Protein: p.Ser597Phe
Coding: c.1790C>T
MANE Select: NM_001005273
Type: single nucleotide variant
Location: chr17:7897165 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 597: the 'disordered' region; a modified residue (phosphoserine); 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-ser597phe (accessed [today's date]).

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