Is ADAT3 p.Pro292Ser (c.874C>T) pathogenic?

ADAT3 p.Pro292Ser (c.874C>T) is classified Uncertain significance in ADAT3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-31). Very rare (popmax 0.00619%, nfe); Associated with intellectual disability-strabismus syndrome.

What condition is associated with ADAT3 p.Pro292Ser (c.874C>T)?

ADAT3 p.Pro292Ser (c.874C>T) is associated with intellectual disability-strabismus syndrome (ClinVar).

How common is ADAT3 p.Pro292Ser (c.874C>T) in the general population?

ADAT3 p.Pro292Ser (c.874C>T) is very rare (popmax 0.00619%, nfe) (gnomAD).

How is Intellectual disability-strabismus syndrome inherited?

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

ADAT3 p.Pro292Ser

c.874C>T · rs772924757 · VCV2438869

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00619%, nfe)

Conditions

intellectual disability-strabismus syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.371	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 1,100 bp · p 7.8e-12 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00619% European (non-Finnish) · 73/1,179,332 alleles

Filtering AF 0.00503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00463%

Overall 0.00484% 78/1,609,994 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00619%	16,155
African / African-American	0.00267%	37,452
Admixed American	0.00167%	59,958
Remaining individualsnot grpmax-eligible	0.0016%	62,398
South Asian	0.0011%	91,078

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.Pro292Ser
Coding: c.874C>T
MANE Select: NM_138422
dbSNP: rs772924757
Type: single nucleotide variant
Location: chr19:1912921 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.83
Residue 292: 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.Pro292Leu Uncertain significance ★★ same residue
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.Thr296= Benign ★★ 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-pro292ser (accessed [today's date]).

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