Is DISC1 p.Pro230= (c.690A>G) pathogenic?

DISC1 p.Pro230= (c.690A>G) is classified Likely benign in DISC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-11). Very rare (popmax 0.00127%, nfe); Associated with DISC1-related disorder.

What condition is associated with DISC1 p.Pro230= (c.690A>G)?

DISC1 p.Pro230= (c.690A>G) is associated with DISC1-related disorder (ClinVar).

How common is DISC1 p.Pro230= (c.690A>G) in the general population?

DISC1 p.Pro230= (c.690A>G) is very rare (popmax 0.00127%, nfe) (gnomAD).

DISC1 p.Pro230=

c.690A>G · rs767632505 · VCV3058709

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00127%, 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 -4.4	GERP -3.6
Overall
CADD	0.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 15/1,180,044 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00109% 16/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)grpmax	0.00127%	78,670

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro230=
Coding: c.690A>G
MANE Select: NM_018662
dbSNP: rs767632505
Type: single nucleotide variant
Location: chr1:231694448 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.74 · 1 PDB
Residue 230: the 'interaction with map1a' region; the 'disordered' 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-pro230 (accessed [today's date]).

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