Is DLGAP1 p.Pro517= (c.1551G>A) pathogenic?

DLGAP1 p.Pro517= (c.1551G>A) is classified Benign in DLGAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-22). Common (popmax 33.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with DLGAP1-related disorder.

What condition is associated with DLGAP1 p.Pro517= (c.1551G>A)?

DLGAP1 p.Pro517= (c.1551G>A) is associated with DLGAP1-related disorder (ClinVar).

DLGAP1 p.Pro517=

Q: How common is DLGAP1 p.Pro517= (c.1551G>A) in the general population?

DLGAP1 p.Pro517= (c.1551G>A) is common (popmax 33.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1551G>A · rs3745051 · VCV3060604

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 33.8%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

DLGAP1-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 -4.9	GERP -4.1
Overall
CADD	6.858	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 33.8% East Asian · 15,147/44,818 alleles

Filtering AF 33.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 33.2%

Overall 13.6% 218,700/1,612,722 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	33.8%	3
African / African-American	30.3%	3
Middle Eastern	22.3%	4
South Asian	21.9%	5
Ashkenazi Jewishnot grpmax-eligible	16.9%	6
Remaining individualsnot grpmax-eligible	15.8%	6
Finnishnot grpmax-eligible	15.2%	7
Admixed American	13.8%	7
Amishnot grpmax-eligible	10.9%	9
European (non-Finnish)	10.7%	9

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: DLGAP1
Protein: p.Pro517=
Coding: c.1551G>A
MANE Select: NM_004746
dbSNP: rs3745051
Type: single nucleotide variant
Location: chr18:3729175 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.85 · 3 PDB

Full DLGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DLGAP1-related disorder

Similar variants

DLGAP1 p.Pro517Ser Uncertain significance ★ ⚠ same residue
DLGAP1 p.Arg340Ter Uncertain significance ★ same condition
DLGAP1 p.Trp810Ter Uncertain significance ★ same condition
DLGAP1 p.Leu269Gln Uncertain significance ⚠ same condition
DLGAP1 p.Thr69Pro Uncertain significance ⚠ same condition
DLGAP1 c.1351-3C>T Likely benign same condition
DLGAP1 c.957+4405C>G Likely benign same condition
DLGAP1 c.957+4506C>T 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/dlgap1-p-pro517 (accessed [today's date]).

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