Is DISP2 p.Ser242Ile (c.725G>T) pathogenic?

DISP2 p.Ser242Ile (c.725G>T) is classified Uncertain significance in DISP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely benign (0.0992); Absent from gnomAD v4.1.

How common is DISP2 p.Ser242Ile (c.725G>T) in the general population?

DISP2 p.Ser242Ile (c.725G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DISP2 p.Ser242Ile (c.725G>T)?

AlphaMissense predicts likely benign (score 0.0992) — an in-silico prediction, not a clinical call.

DISP2 p.Ser242Ile

c.725G>T · rs752216408 · VCV3082620

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0992 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0992	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -8.68	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 0.029	GERP -2.5
Regional constraint	o/e 0.94	unconstrained · MANE · 6,941 bp · p 0.24 · regional, not allelic
Overall
CADD	0.866	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

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: DISP2
Protein: p.Ser242Ile
Coding: c.725G>T
MANE Select: NM_033510
dbSNP: rs752216408
Type: single nucleotide variant
Location: chr15:40365152 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.24
Residue 242: the 'disordered' region

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

Similar variants

DISP2 p.Ser242Thr Uncertain significance ★ ⚠ same residue
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

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-ser242ile (accessed [today's date]).

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