Is DISP2 p.Arg852His (c.2555G>A) pathogenic?

DISP2 p.Arg852His (c.2555G>A) is classified Uncertain significance in DISP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.0819); Very rare (popmax 0.00229%, nfe).

How common is DISP2 p.Arg852His (c.2555G>A) in the general population?

DISP2 p.Arg852His (c.2555G>A) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about DISP2 p.Arg852His (c.2555G>A)?

AlphaMissense predicts likely benign (score 0.0819) — an in-silico prediction, not a clinical call.

DISP2 p.Arg852His

c.2555G>A · VCV4240852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0819 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0819	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -7.16	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 4.5	GERP 0.045, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 918 bp · p 8.8e-05 · 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 0.00229% European (non-Finnish) · 27/1,179,990 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.0018% 29/1,611,244 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,703
Finnishnot grpmax-eligible	0.00163%	61,310
Remaining individualsnot grpmax-eligible	0.0016%	62,454

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.Arg852His
Coding: c.2555G>A
MANE Select: NM_033510
Type: single nucleotide variant
Location: chr15:40368667 (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-arg852his (accessed [today's date]).

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