Is DLGAP1 p.Pro516= (c.1548G>A) pathogenic?

DLGAP1 p.Pro516= (c.1548G>A) is classified Likely benign in DLGAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-20). Ultra-rare (popmax 0.0825%, mid); Associated with DLGAP1-related disorder.

What condition is associated with DLGAP1 p.Pro516= (c.1548G>A)?

DLGAP1 p.Pro516= (c.1548G>A) is associated with DLGAP1-related disorder (ClinVar).

How common is DLGAP1 p.Pro516= (c.1548G>A) in the general population?

DLGAP1 p.Pro516= (c.1548G>A) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

DLGAP1 p.Pro516=

c.1548G>A · rs146904332 · VCV3055806

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

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 -7.9	GERP -4.4
Overall
CADD	2.017	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% Middle Eastern · 5/6,058 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00477% 77/1,613,132 alleles · ultra-rare exomes 66/1,460,968 · genomes 11/152,164 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
European (non-Finnish)	0.00551%	18,150
African / African-American	0.004%	24,974
Remaining individualsnot grpmax-eligible	0.0032%	31,217
Admixed American	0.00167%	59,956
South Asian	0.0011%	90,934

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.Pro516=
Coding: c.1548G>A
MANE Select: NM_004746
dbSNP: rs146904332
Type: single nucleotide variant
Location: chr18:3729178 (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.Pro516Leu 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-pro516 (accessed [today's date]).

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