Is DLGAP4 p.Ser614Arg (c.1842C>G) pathogenic?

DLGAP4 p.Ser614Arg (c.1842C>G) is classified Uncertain significance in DLGAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely pathogenic (0.8886); Absent from gnomAD v4.1.

How common is DLGAP4 p.Ser614Arg (c.1842C>G) in the general population?

DLGAP4 p.Ser614Arg (c.1842C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLGAP4 p.Ser614Arg (c.1842C>G)?

AlphaMissense predicts likely pathogenic (score 0.8886) — an in-silico prediction, not a clinical call.

DLGAP4 p.Ser614Arg

c.1842C>G · rs1454091116 · VCV3082858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8886 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8886	likely pathogenic
REVEL	0.217	benign-leaning
SaProt	LLR -8.00	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 4.1	GERP 2.8, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 95 kb · p 8.8e-13 · regional, not allelic
Overall
CADD	25.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DLGAP4
Protein: p.Ser614Arg
Coding: c.1842C>G
MANE Select: NM_001365621
dbSNP: rs1454091116
Type: single nucleotide variant
Location: chr20:36496898 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.01
Residue 614: 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-ser614arg (accessed [today's date]).

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