Is DLGAP2 p.Glu678= (c.2034A>G) pathogenic?

DLGAP2 p.Glu678= (c.2034A>G) is classified Benign in DLGAP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-09-24). Common (popmax 71.7%, afr) — too common for a highly-penetrant pathogenic allele.

DLGAP2 p.Glu678=

Q: How common is DLGAP2 p.Glu678= (c.2034A>G) in the general population?

DLGAP2 p.Glu678= (c.2034A>G) is common (popmax 71.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2034A>G · rs2235112 · VCV1264860

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 71.7%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.183	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.89	GERP -4.4, phastCons 1
Overall
CADD	0.922	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 71.7% African / African-American · 53,194/74,216 alleles

Filtering AF 71.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 71%

Overall 31.2% 495,914/1,588,270 alleles · common exomes 431,310/1,436,348 · genomes 64,604/151,922 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	71.7%	1
East Asian	58.4%	2
Admixed American	49.7%	2
Middle Eastern	47.8%	2
South Asian	46.9%	2
Ashkenazi Jewishnot grpmax-eligible	35.3%	3
Remaining individualsnot grpmax-eligible	34.2%	3
Finnishnot grpmax-eligible	27.6%	4
European (non-Finnish)	25.4%	4
Amishnot grpmax-eligible	24.7%	4

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: DLGAP2
Protein: p.Glu678=
Coding: c.2034A>G
MANE Select: NM_001346810
dbSNP: rs2235112
Type: single nucleotide variant
Location: chr8:1668552 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 48.83

Full DLGAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLGAP2 c.1810+14A>G Benign ★★ same type
DLGAP2 c.2160+19C>G Benign ★★ same type
DLGAP2 p.Pro464Gln Benign ★★ same type
DLGAP2 c.2203-7G>T Uncertain significance ★ same type
DLGAP2 p.Ala1019Gly Uncertain significance ★ ⚠ same type
DLGAP2 p.Ala1026Val Uncertain significance ★ same type
DLGAP2 p.Ala116Thr Uncertain significance ★ ⚠ same type
DLGAP2 p.Ala177Thr 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/dlgap2-p-glu678 (accessed [today's date]).

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