Is DISP2 p.Cys697Arg (c.2089T>C) pathogenic?

DISP2 p.Cys697Arg (c.2089T>C) is classified Uncertain significance in DISP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-12). AlphaMissense: likely pathogenic (0.8888); Ultra-rare (popmax 0.0171%, mid).

How common is DISP2 p.Cys697Arg (c.2089T>C) in the general population?

DISP2 p.Cys697Arg (c.2089T>C) is ultra-rare (popmax 0.0171%, mid) (gnomAD).

What do computational predictors say about DISP2 p.Cys697Arg (c.2089T>C)?

AlphaMissense predicts likely pathogenic (score 0.8888) — an in-silico prediction, not a clinical call.

DISP2 p.Cys697Arg

c.2089T>C · rs1173186288 · VCV3082605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8888 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8888	likely pathogenic · top 7% in DISP2
REVEL	0.465	indeterminate
SaProt	LLR -3.77	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 2,889 bp · p 0.52 · regional, not allelic
Overall
CADD	27.9	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 0.0171% Middle Eastern · 1/5,860 alleles

Overall 6.87e-05% 1/1,455,948 alleles · ultra-rare

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: DISP2
Protein: p.Cys697Arg
Coding: c.2089T>C
MANE Select: NM_033510
dbSNP: rs1173186288
Type: single nucleotide variant
Location: chr15:40368201 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.24

Full DISP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DISP2 p.Pro194= Benign ★★ same type
DISP2 p.Ala1053Thr Uncertain significance ★ ⚠ same type
DISP2 p.Ala1069Gly Uncertain significance ★ ⚠ same type
DISP2 p.Ala1128Ser Uncertain significance ★ ⚠ same type
DISP2 p.Ala1128Val Uncertain significance ★ ⚠ same type
DISP2 p.Ala1210Gly Uncertain significance ★ ⚠ same type
DISP2 p.Ala1343Pro Uncertain significance ★ ⚠ same type
DISP2 p.Ala1343Val 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/disp2-p-cys697arg (accessed [today's date]).

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