Is CHD3 p.Ile1302Thr (c.3905T>C) pathogenic?

CHD3 p.Ile1302Thr (c.3905T>C) is classified Uncertain significance in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-31). AlphaMissense: likely pathogenic (0.6397); Very rare (popmax 0.00501%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHD3 p.Ile1302Thr (c.3905T>C)?

CHD3 p.Ile1302Thr (c.3905T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CHD3 p.Ile1302Thr (c.3905T>C) in the general population?

CHD3 p.Ile1302Thr (c.3905T>C) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about CHD3 p.Ile1302Thr (c.3905T>C)?

AlphaMissense predicts likely pathogenic (score 0.6397) — an in-silico prediction, not a clinical call.

CHD3 p.Ile1302Thr

c.3905T>C · VCV3266845

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6397 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6397	likely pathogenic
REVEL	0.445	indeterminate
SaProt	LLR -4.48	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; 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	24.6	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 0.00501% Admixed American · 3/59,894 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000274% 4/1,460,698 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,965
European (non-Finnish)	8.48e-05%	1,179,067

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.Ile1302Thr
Coding: c.3905T>C
MANE Select: NM_001005273
Type: single nucleotide variant
Location: chr17:7904452 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1302: 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-ile1302thr (accessed [today's date]).

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