Is DISC1 p.Arg345Gln (c.1034G>A) pathogenic?

DISC1 p.Arg345Gln (c.1034G>A) is classified Benign in DISC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0617); Low-frequency (popmax 1.27%, eas).

How common is DISC1 p.Arg345Gln (c.1034G>A) in the general population?

DISC1 p.Arg345Gln (c.1034G>A) is low-frequency (popmax 1.27%, eas) (gnomAD).

What do computational predictors say about DISC1 p.Arg345Gln (c.1034G>A)?

AlphaMissense predicts likely benign (score 0.0617) — an in-silico prediction, not a clinical call.

DISC1 p.Arg345Gln

c.1034G>A · rs77080351 · VCV713043

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0617 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.27%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0617	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -6.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -3.9
Regional constraint	o/e 0.78	unconstrained · MANE · 77 kb · p 8.4e-06 · regional, not allelic
Overall
CADD	0.084	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 1.27% East Asian · 571/44,866 alleles

Filtering AF 1.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.15%

Overall 0.0441% 711/1,613,626 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.27%	79
Remaining individualsnot grpmax-eligible	0.138%	727
African / African-American	0.0173%	5,774
Middle Eastern	0.0165%	6,060
South Asian	0.0121%	8,276
Admixed American	0.00667%	15,001
European (non-Finnish)	0.00203%	49,166
Finnishnot grpmax-eligible	0.00157%	63,612

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.Arg345Gln
Coding: c.1034G>A
MANE Select: NM_018662
dbSNP: rs77080351
Type: single nucleotide variant
Location: chr1:231694792 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.74 · 1 PDB
Residue 345: the 'interaction with traf3ip1' region

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

Similar variants

DISC1 p.Arg345Trp Uncertain significance ★ ⚠ same residue
DISC1 p.Cys187Tyr Uncertain significance ★★ ⚠ same type
DISC1 p.Arg170Cys Benign ★★ same type
DISC1 p.Glu751Gln Benign ★★ same type
DISC1 p.Leu330Phe Benign ★★ ⚠ same type
DISC1 p.Pro432Leu Likely benign ★★ same type
DISC1 p.Ala13Thr Uncertain significance ★ ⚠ same type
DISC1 p.Ala220Val Uncertain significance ★ ⚠ same type

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-arg345gln (accessed [today's date]).

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