Is DLGAP2 p.His180Pro (c.539A>C) pathogenic?

DLGAP2 p.His180Pro (c.539A>C) is classified Uncertain significance in DLGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-28). AlphaMissense: likely benign (0.0569); Very rare (popmax 0.00195%, nfe).

How common is DLGAP2 p.His180Pro (c.539A>C) in the general population?

DLGAP2 p.His180Pro (c.539A>C) is very rare (popmax 0.00195%, nfe) (gnomAD).

What do computational predictors say about DLGAP2 p.His180Pro (c.539A>C)?

AlphaMissense predicts likely benign (score 0.0569) — an in-silico prediction, not a clinical call.

DLGAP2 p.His180Pro

c.539A>C · rs757352058 · VCV2341057

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0569 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0569	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -4.51	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 6.8	GERP -0.53, phastCons 1
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM H179P vs ClinVar H180P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% European (non-Finnish) · 23/1,179,120 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00159% 23/1,446,858 alleles · very rare

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.His180Pro
Coding: c.539A>C
MANE Select: NM_001346810
dbSNP: rs757352058
Type: single nucleotide variant
Location: chr8:1548992 (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.Glu678= 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

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-his180pro (accessed [today's date]).

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