Is DLGAP4 p.Pro572Leu (c.1715C>T) pathogenic?

DLGAP4 p.Pro572Leu (c.1715C>T) is classified Uncertain significance in DLGAP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-11). AlphaMissense: likely pathogenic (0.9822); Very rare (popmax 0.00878%, sas).

How common is DLGAP4 p.Pro572Leu (c.1715C>T) in the general population?

DLGAP4 p.Pro572Leu (c.1715C>T) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about DLGAP4 p.Pro572Leu (c.1715C>T)?

AlphaMissense predicts likely pathogenic (score 0.9822) — an in-silico prediction, not a clinical call.

DLGAP4 p.Pro572Leu

c.1715C>T · rs750688838 · VCV2377465

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9822 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9822	likely pathogenic · top 7% in DLGAP4
REVEL	0.444	indeterminate
SaProt	LLR -6.89	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, 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 0.00878% South Asian · 8/91,086 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00287% 42/1,461,704 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,386
Admixed American	0.00333%	30,010
Remaining individualsnot grpmax-eligible	0.0032%	31,251
European (non-Finnish)	0.00254%	39,330

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.Pro572Leu
Coding: c.1715C>T
MANE Select: NM_001365621
dbSNP: rs750688838
Type: single nucleotide variant
Location: chr20:36496771 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.01
Residue 572: the 'disordered' region

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

Similar variants

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
DLGAP4 p.Ala161Val 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-pro572leu (accessed [today's date]).

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