Is ADAT3 p.Thr296= (c.888T>C) pathogenic?

ADAT3 p.Thr296= (c.888T>C) is classified Benign in ADAT3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-07-14). Common (popmax 46.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with intellectual disability-strabismus syndrome.

What condition is associated with ADAT3 p.Thr296= (c.888T>C)?

ADAT3 p.Thr296= (c.888T>C) is associated with intellectual disability-strabismus syndrome (ClinVar).

How is Intellectual disability-strabismus syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ADAT3 p.Thr296=

Q: How common is ADAT3 p.Thr296= (c.888T>C) in the general population?

ADAT3 p.Thr296= (c.888T>C) is common (popmax 46.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.888T>C · rs12984675 · VCV1185542

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 46.5%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

intellectual disability-strabismus syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -2.8
Overall
CADD	0.068	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 46.5% East Asian · 20,732/44,620 alleles

Filtering AF 45.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 45.7%

Overall 19.6% 312,010/1,588,924 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	46.5%	2
African / African-American	44.7%	2
Admixed American	38.1%	3
South Asian	27.6%	4
Middle Eastern	26.8%	4
Finnishnot grpmax-eligible	26.7%	4
Remaining individualsnot grpmax-eligible	21.5%	5
Ashkenazi Jewishnot grpmax-eligible	21.3%	5
Amishnot grpmax-eligible	16%	6
European (non-Finnish)	14.9%	7

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: ADAT3
Protein: p.Thr296=
Coding: c.888T>C
MANE Select: NM_138422
dbSNP: rs12984675
Type: single nucleotide variant
Location: chr19:1912935 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.83
Residue 296: the cmp/dcmp-type deaminase domain

Full ADAT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability-strabismus syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Intellectual disability-strabismus syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ADAT3 p.Val144Met Pathogenic/Likely pathogenic ★★ same condition
ADAT3 p.Ala20Val Uncertain significance ★★ same condition
ADAT3 p.Arg250Cys Uncertain significance ★★ same condition
ADAT3 p.Gly251Ser Uncertain significance ★★ same condition
ADAT3 p.Pro292Leu Uncertain significance ★★ same condition
ADAT3 p.Pro292Ser Uncertain significance ★★ same condition
ADAT3 p.Glu107Lys Likely pathogenic ★ same condition
ADAT3 p.Ala113Gly 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/adat3-p-thr296 (accessed [today's date]).

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