Is DLGAP4 p.Arg73His (c.218G>A) pathogenic?

DLGAP4 p.Arg73His (c.218G>A) is classified Uncertain significance in DLGAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: ambiguous (0.4572); Very rare (popmax 0.00525%, nfe).

How common is DLGAP4 p.Arg73His (c.218G>A) in the general population?

DLGAP4 p.Arg73His (c.218G>A) is very rare (popmax 0.00525%, nfe) (gnomAD).

What do computational predictors say about DLGAP4 p.Arg73His (c.218G>A)?

AlphaMissense predicts ambiguous (score 0.4572) — an in-silico prediction, not a clinical call.

DLGAP4 p.Arg73His

c.218G>A · VCV3840358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4572 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00525%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4572	ambiguous
REVEL	0.562	indeterminate
SaProt	LLR -7.85	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.7, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 95 kb · p 8.8e-13 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00525% European (non-Finnish) · 62/1,180,020 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00428% 69/1,613,912 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00525%	19,033
Finnishnot grpmax-eligible	0.00469%	21,335
Remaining individualsnot grpmax-eligible	0.0032%	31,244
Admixed American	0.00167%	59,996
South Asian	0.0011%	91,068

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: DLGAP4
Protein: p.Arg73His
Coding: c.218G>A
MANE Select: NM_001365621
Type: single nucleotide variant
Location: chr20:36431935 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.01

Full DLGAP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLGAP4 p.Pro572Leu Uncertain significance ★★ ⚠ same type
DLGAP4 p.Ala845= Benign ★★ same type
DLGAP4 p.Gly540Ser Likely benign ★★ same type
DLGAP4 p.Pro270= Likely benign ★★ same type
DLGAP4 c.2011-343A>T Uncertain significance ★ same type
DLGAP4 p.Ala131Thr Uncertain significance ★ ⚠ same type
DLGAP4 p.Ala154Pro Uncertain significance ★ ⚠ same type
DLGAP4 p.Ala154Ser 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/dlgap4-p-arg73his (accessed [today's date]).

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