Is DISC1 p.Glu834= (c.2502G>A) pathogenic?

DISC1 p.Glu834= (c.2502G>A) is classified Likely benign in DISC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-19). Ultra-rare (popmax 0.088%, nfe); Associated with DISC1-related disorder.

What condition is associated with DISC1 p.Glu834= (c.2502G>A)?

DISC1 p.Glu834= (c.2502G>A) is associated with DISC1-related disorder (ClinVar).

How common is DISC1 p.Glu834= (c.2502G>A) in the general population?

DISC1 p.Glu834= (c.2502G>A) is ultra-rare (popmax 0.088%, nfe) (gnomAD).

DISC1 p.Glu834=

c.2502G>A · rs41271517 · VCV3042182

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.088%, nfe)

Conditions

DISC1-related disorder

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 3.1	GERP 0.27, phastCons 1
Overall
CADD	2.881	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.088% European (non-Finnish) · 1,034/1,175,198 alleles

Filtering AF 0.0835% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0817%

Overall 0.0693% 1,114/1,606,858 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.088%	1,137
Remaining individualsnot grpmax-eligible	0.0483%	2,071
Ashkenazi Jewishnot grpmax-eligible	0.034%	2,941
Finnishnot grpmax-eligible	0.0235%	4,255
African / African-American	0.0213%	4,685
Admixed American	0.0134%	7,469
South Asian	0.00111%	89,966

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: DISC1
Protein: p.Glu834=
Coding: c.2502G>A
MANE Select: NM_018662
dbSNP: rs41271517
Type: single nucleotide variant
Location: chr1:232036768 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.74 · 1 PDB
Residue 834: the 'interaction with pafah1b1' region; the 'interaction with ndel1' region; the 'necessary and sufficient for interaction with pcnt and localization at the centrosome' region; the 'interaction with atf4 and atf5' region

Full DISC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DISC1-related disorder

Similar variants

DISC1 p.Cys187Tyr Uncertain significance ★★ ⚠ same condition
DISC1 p.Arg454Ile Uncertain significance ★ ⚠ same condition
DISC1 p.Ile773= Uncertain significance ★ same condition
DISC1 p.Pro231Ser Uncertain significance ★ ⚠ same condition
DISC1 p.Gln498Pro Uncertain significance ⚠ same condition
DISC1 c.1117+18828G>A Likely benign same condition
DISC1 c.1634+13T>G Likely benign same condition
DISC1 c.1981+48069C>G Benign 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/disc1-p-glu834 (accessed [today's date]).

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