Is DLGAP1 p.Phe730Leu (c.2188T>C) pathogenic?

DLGAP1 p.Phe730Leu (c.2188T>C) is classified Uncertain significance in DLGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely pathogenic (0.6); Absent from gnomAD v4.1.

How common is DLGAP1 p.Phe730Leu (c.2188T>C) in the general population?

DLGAP1 p.Phe730Leu (c.2188T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLGAP1 p.Phe730Leu (c.2188T>C)?

AlphaMissense predicts likely pathogenic (score 0.6) — an in-silico prediction, not a clinical call.

DLGAP1 p.Phe730Leu

c.2188T>C · VCV4660382

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6	likely pathogenic
REVEL	0.028	moderately benign-leaning
SaProt	LLR -4.74	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 9.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 380 kb · p 2.6e-26 · regional, not allelic
Overall
CADD	23.8	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: DLGAP1
Protein: p.Phe730Leu
Coding: c.2188T>C
MANE Select: NM_004746
Type: single nucleotide variant
Location: chr18:3534485 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.85 · 3 PDB

Full DLGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLGAP1 p.Ala659= Benign ★★ same type
DLGAP1 p.Pro824= Benign ★★ same type
DLGAP1 p.Ser296= Benign ★★ same type
DLGAP1 p.Thr284= Benign ★★ same type
DLGAP1 p.Thr624= Benign ★★ same type
DLGAP1 p.Ala173Val Uncertain significance ★ ⚠ same type
DLGAP1 p.Ala189Thr Uncertain significance ★ ⚠ same type
DLGAP1 p.Ala302Val 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/dlgap1-p-phe730leu (accessed [today's date]).

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