Is DISC1 p.Arg170Cys (c.508C>T) pathogenic?

DISC1 p.Arg170Cys (c.508C>T) is classified Benign in DISC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1188); Rare (popmax 0.986%, amr).

How common is DISC1 p.Arg170Cys (c.508C>T) in the general population?

DISC1 p.Arg170Cys (c.508C>T) is rare (popmax 0.986%, amr) (gnomAD).

What do computational predictors say about DISC1 p.Arg170Cys (c.508C>T)?

AlphaMissense predicts likely benign (score 0.1188) — an in-silico prediction, not a clinical call.

DISC1 p.Arg170Cys

c.508C>T · rs186593988 · VCV783018

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1188 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.986%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1188	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -7.28	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 -0.044	GERP -3.5
Regional constraint	o/e 1.04	unconstrained · MANE · 68 kb · p 0.48 · regional, not allelic
Overall
CADD	16.61	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 0.986% Admixed American · 592/60,034 alleles

Filtering AF 0.92% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.894%

Overall 0.0416% 672/1,614,250 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.986%	101
African / African-American	0.036%	2,780
Remaining individualsnot grpmax-eligible	0.0336%	2,977
European (non-Finnish)	0.00271%	36,877

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.Arg170Cys
Coding: c.508C>T
MANE Select: NM_018662
dbSNP: rs186593988
Type: single nucleotide variant
Location: chr1:231694266 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.74 · 1 PDB
Residue 170: the 'interaction with map1a' region

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

Similar variants

DISC1 p.Cys187Tyr Uncertain significance ★★ ⚠ same type
DISC1 p.Arg345Gln 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
DISC1 p.Ala235Ser 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-arg170cys (accessed [today's date]).

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