Is DISP3 p.Pro999= (c.2997G>A) pathogenic?

DISP3 p.Pro999= (c.2997G>A) is classified Benign in DISP3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-21). Common (popmax 42.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with DISP3-related disorder.

What condition is associated with DISP3 p.Pro999= (c.2997G>A)?

DISP3 p.Pro999= (c.2997G>A) is associated with DISP3-related disorder (ClinVar).

DISP3 p.Pro999=

Q: How common is DISP3 p.Pro999= (c.2997G>A) in the general population?

DISP3 p.Pro999= (c.2997G>A) is common (popmax 42.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2997G>A · rs2076468 · VCV3059972

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 42.9%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

DISP3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -2.4
Overall
CADD	0.241	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42.9% East Asian · 19,261/44,850 alleles

Filtering AF 42.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.2%

Overall 14.7% 237,495/1,613,910 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	42.9%	2
South Asian	19.3%	5
Ashkenazi Jewishnot grpmax-eligible	15.7%	6
Remaining individualsnot grpmax-eligible	15.1%	7
European (non-Finnish)	14%	7
Finnishnot grpmax-eligible	12.8%	8
Middle Eastern	10.9%	9
Admixed American	9.29%	11
African / African-American	9%	11
Amishnot grpmax-eligible	8.11%	12

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: DISP3
Protein: p.Pro999=
Coding: c.2997G>A
MANE Select: NM_020780
dbSNP: rs2076468
Type: single nucleotide variant
Location: chr1:11529854 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.84

Full DISP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DISP3-related disorder

Similar variants

DISP3 c.1749+5G>A Likely benign same condition
DISP3 c.3230-4G>A Likely benign same condition
DISP3 p.Ala1000= Likely benign same condition
DISP3 p.Ala1297= Benign same condition
DISP3 p.Ala650Thr Benign same condition
DISP3 p.Arg1022His Likely benign same condition
DISP3 p.Arg166Gln Likely benign same condition
DISP3 p.Arg294= Likely benign same condition

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/disp3-p-pro999 (accessed [today's date]).

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