Is DLGAP1 p.Ser18Leu (c.53C>T) pathogenic?

DLGAP1 p.Ser18Leu (c.53C>T) is classified Uncertain significance in DLGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely benign (0.0666); Very rare (popmax 0.00153%, nfe).

How common is DLGAP1 p.Ser18Leu (c.53C>T) in the general population?

DLGAP1 p.Ser18Leu (c.53C>T) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about DLGAP1 p.Ser18Leu (c.53C>T)?

AlphaMissense predicts likely benign (score 0.0666) — an in-silico prediction, not a clinical call.

DLGAP1 p.Ser18Leu

c.53C>T · VCV3502365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0666 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0666	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -7.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 946 bp · p 0.15 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00153% European (non-Finnish) · 18/1,179,888 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00118% 19/1,608,586 alleles · very rare exomes 17/1,456,400 · genomes 2/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00153%	65,549
South Asian	0.0011%	91,026

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: DLGAP1
Protein: p.Ser18Leu
Coding: c.53C>T
MANE Select: NM_004746
Type: single nucleotide variant
Location: chr18:3880016 (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-ser18leu (accessed [today's date]).

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