Is DLGAP2 p.Ser245Leu (c.734C>T) pathogenic?

DLGAP2 p.Ser245Leu (c.734C>T) is classified Uncertain significance in DLGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-15). AlphaMissense: likely pathogenic (0.6604); Very rare (popmax 8.52e-05%, nfe).

How common is DLGAP2 p.Ser245Leu (c.734C>T) in the general population?

DLGAP2 p.Ser245Leu (c.734C>T) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

What do computational predictors say about DLGAP2 p.Ser245Leu (c.734C>T)?

AlphaMissense predicts likely pathogenic (score 0.6604) — an in-silico prediction, not a clinical call.

DLGAP2 p.Ser245Leu

c.734C>T · rs1331541047 · VCV2619234

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6604 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6604	likely pathogenic
REVEL	0.443	indeterminate
SaProt	LLR -13.03	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 8.6, phastCons 1
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S244L vs ClinVar S245L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.52e-05% European (non-Finnish) · 1/1,173,886 alleles

Overall 0.000657% 1/152,202 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: DLGAP2
Protein: p.Ser245Leu
Coding: c.734C>T
MANE Select: NM_001346810
dbSNP: rs1331541047
Type: single nucleotide variant
Location: chr8:1549187 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 48.83
Residue 245: the 'disordered' region

Full DLGAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLGAP2 c.1810+14A>G Benign ★★ same type
DLGAP2 c.2160+19C>G Benign ★★ same type
DLGAP2 p.Glu678= Benign ★★ same type
DLGAP2 p.Pro464Gln Benign ★★ same type
DLGAP2 c.2203-7G>T Uncertain significance ★ same type
DLGAP2 p.Ala1019Gly Uncertain significance ★ ⚠ same type
DLGAP2 p.Ala1026Val Uncertain significance ★ ⚠ same type
DLGAP2 p.Ala116Thr 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/dlgap2-p-ser245leu (accessed [today's date]).

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