Is DISP2 p.Pro194= (c.582C>T) pathogenic?

DISP2 p.Pro194= (c.582C>T) is classified Benign in DISP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-07). Low-frequency (popmax 2.54%, afr).

How common is DISP2 p.Pro194= (c.582C>T) in the general population?

DISP2 p.Pro194= (c.582C>T) is low-frequency (popmax 2.54%, afr) (gnomAD).

DISP2 p.Pro194=

c.582C>T · rs72733418 · VCV720007

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.54%, afr)

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 -7.7	GERP -3.7
Overall
CADD	0.325	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.54% African / African-American · 1,909/75,046 alleles

Filtering AF 2.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.41%

Overall 0.777% 12,541/1,613,772 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.73%	27
African / African-Americangrpmax	2.54%	39
European (non-Finnish)	0.821%	122
Remaining individualsnot grpmax-eligible	0.653%	153
Finnishnot grpmax-eligible	0.411%	243
Admixed American	0.245%	408
Ashkenazi Jewishnot grpmax-eligible	0.152%	658
Middle Eastern	0.115%	866
South Asian	0.0406%	2,462

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro194=
Coding: c.582C>T
MANE Select: NM_033510
dbSNP: rs72733418
Type: single nucleotide variant
Location: chr15:40364523 (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.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
DISP2 p.Ala1355Thr 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-pro194 (accessed [today's date]).

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