Is DLGAP2 p.Pro464Gln (c.1391C>A) pathogenic?

DLGAP2 p.Pro464Gln (c.1391C>A) is classified Benign in DLGAP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-05-14). AlphaMissense: likely benign (0.0837); Common (popmax 61.4%, amr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DLGAP2 p.Pro464Gln (c.1391C>A)?

AlphaMissense predicts likely benign (score 0.0837) — an in-silico prediction, not a clinical call.

DLGAP2 p.Pro464Gln

Q: How common is DLGAP2 p.Pro464Gln (c.1391C>A) in the general population?

DLGAP2 p.Pro464Gln (c.1391C>A) is common (popmax 61.4%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1391C>A · rs2301963 · VCV1272088

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0837 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 61.4%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0837	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -6.77	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 5.7	GERP 6.1, phastCons 1
Overall
CADD	21.4	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 P463Q vs ClinVar P464Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 61.4% Admixed American · 36,673/59,686 alleles

Filtering AF 60.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 60.7%

Overall 45.7% 736,784/1,611,828 alleles · common exomes 668,871/1,459,882 · genomes 67,913/151,946 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	61.4%	2
Middle Eastern	57%	2
South Asian	55.6%	2
Amishnot grpmax-eligible	48.3%	2
Ashkenazi Jewishnot grpmax-eligible	48.3%	2
East Asian	47.7%	2
Remaining individualsnot grpmax-eligible	46.9%	2
European (non-Finnish)	44.6%	2
Finnishnot grpmax-eligible	40.4%	2
African / African-American	39%	3

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.Pro464Gln
Coding: c.1391C>A
MANE Select: NM_001346810
dbSNP: rs2301963
Type: single nucleotide variant
Location: chr8:1565843 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 48.83
Residue 463 UniProt numbering: the 'disordered' region

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.Glu678= 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-pro464gln (accessed [today's date]).

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