Is DISP2 p.Arg97Trp (c.289C>T) pathogenic?

DISP2 p.Arg97Trp (c.289C>T) is classified Uncertain significance in DISP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: likely benign (0.0905); Ultra-rare (popmax 0.0547%, afr).

How common is DISP2 p.Arg97Trp (c.289C>T) in the general population?

DISP2 p.Arg97Trp (c.289C>T) is ultra-rare (popmax 0.0547%, afr) (gnomAD).

What do computational predictors say about DISP2 p.Arg97Trp (c.289C>T)?

AlphaMissense predicts likely benign (score 0.0905) — an in-silico prediction, not a clinical call.

DISP2 p.Arg97Trp

c.289C>T · rs139247330 · VCV2412379

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0905 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0547%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0905	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -7.47	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 0.24	GERP -0.53, phastCons 0.001
Regional constraint	o/e 0.94	unconstrained · MANE · 6,941 bp · p 0.24 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0547% African / African-American · 41/74,934 alleles

Filtering AF 0.0414% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0368%

Overall 0.00403% 65/1,612,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0547%	1,828
Remaining individualsnot grpmax-eligible	0.00961%	10,408
Admixed American	0.00668%	14,968
South Asian	0.0044%	22,735
Finnishnot grpmax-eligible	0.00156%	64,016
European (non-Finnish)	0.000763%	131,041

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.Arg97Trp
Coding: c.289C>T
MANE Select: NM_033510
dbSNP: rs139247330
Type: single nucleotide variant
Location: chr15:40363794 (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-arg97trp (accessed [today's date]).

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