Is DLGAP2 p.Arg713His (c.2138G>A) pathogenic?

DLGAP2 p.Arg713His (c.2138G>A) is classified Likely benign in DLGAP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-11). AlphaMissense: likely benign (0.0713); Rare (popmax 0.188%, sas); Associated with DLGAP2-related disorder.

What condition is associated with DLGAP2 p.Arg713His (c.2138G>A)?

DLGAP2 p.Arg713His (c.2138G>A) is associated with DLGAP2-related disorder (ClinVar).

How common is DLGAP2 p.Arg713His (c.2138G>A) in the general population?

DLGAP2 p.Arg713His (c.2138G>A) is rare (popmax 0.188%, sas) (gnomAD).

What do computational predictors say about DLGAP2 p.Arg713His (c.2138G>A)?

AlphaMissense predicts likely benign (score 0.0713) — an in-silico prediction, not a clinical call.

DLGAP2 p.Arg713His

c.2138G>A · rs535837045 · VCV3048141

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0713 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.188%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DLGAP2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0713	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -7.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -2.2, phastCons 1
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R712H vs ClinVar R713H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.188% South Asian · 160/85,100 alleles

Filtering AF 0.164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.155%

Overall 0.0111% 174/1,570,964 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.188%	532
Remaining individualsnot grpmax-eligible	0.00494%	20,256
African / African-American	0.0027%	36,994
Admixed American	0.00183%	54,684
European (non-Finnish)	0.000691%	144,687

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.Arg713His
Coding: c.2138G>A
MANE Select: NM_001346810
dbSNP: rs535837045
Type: single nucleotide variant
Location: chr8:1668656 (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

Disease context

DLGAP2-related disorder

Similar variants

DLGAP2 p.Glu892Gln Uncertain significance ★ ⚠ same condition
DLGAP2 p.Asn662Thr Uncertain significance ⚠ same condition
DLGAP2 p.Leu192Val Uncertain significance ⚠ same condition
DLGAP2 p.Ser85Cys Uncertain significance ⚠ same condition
DLGAP2 c.107-10G>C Likely benign same condition
DLGAP2 c.1231-10C>G Likely benign same condition
DLGAP2 c.1810+10C>T Likely benign same condition
DLGAP2 c.2202+9C>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/dlgap2-p-arg713his (accessed [today's date]).

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