Is DLGAP4 p.Pro782Ser (c.2344C>T) pathogenic?

DLGAP4 p.Pro782Ser (c.2344C>T) is classified Uncertain significance in DLGAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). AlphaMissense: likely pathogenic (0.8706); Very rare (popmax 0.0019%, nfe).

How common is DLGAP4 p.Pro782Ser (c.2344C>T) in the general population?

DLGAP4 p.Pro782Ser (c.2344C>T) is very rare (popmax 0.0019%, nfe) (gnomAD).

What do computational predictors say about DLGAP4 p.Pro782Ser (c.2344C>T)?

AlphaMissense predicts likely pathogenic (score 0.8706) — an in-silico prediction, not a clinical call.

DLGAP4 p.Pro782Ser

c.2344C>T · rs2517898879 · VCV2246376

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8706 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0019%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8706	likely pathogenic
REVEL	0.242	benign-leaning
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 95 kb · p 8.8e-13 · regional, not allelic
Overall
CADD	29.0	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 0.0019% European (non-Finnish) · 22/1,160,356 alleles

Filtering AF 0.00124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.00154% 22/1,426,432 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: DLGAP4
Protein: p.Pro782Ser
Coding: c.2344C>T
MANE Select: NM_001365621
dbSNP: rs2517898879
Type: single nucleotide variant
Location: chr20:36500443 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.01
Residue 782: the 'disordered' region

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-pro782ser (accessed [today's date]).

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