Is DISC1 p.Phe210Ser (c.629T>C) pathogenic?

DISC1 p.Phe210Ser (c.629T>C) is classified Uncertain significance in DISC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-25). AlphaMissense: likely pathogenic (0.9246); Absent from gnomAD v4.1.

How common is DISC1 p.Phe210Ser (c.629T>C) in the general population?

DISC1 p.Phe210Ser (c.629T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DISC1 p.Phe210Ser (c.629T>C)?

AlphaMissense predicts likely pathogenic (score 0.9246) — an in-silico prediction, not a clinical call.

DISC1 p.Phe210Ser

c.629T>C · VCV4011857

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9246 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9246	likely pathogenic · top 1% in DISC1
REVEL	0.196	benign-leaning
SaProt	LLR -3.46	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 77 kb · p 8.4e-06 · regional, not allelic
Overall
CADD	25.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DISC1
Protein: p.Phe210Ser
Coding: c.629T>C
MANE Select: NM_018662
Type: single nucleotide variant
Location: chr1:231694387 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.74 · 1 PDB
Residue 210: 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.Arg170Cys Benign ★★ 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

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-phe210ser (accessed [today's date]).

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