Is DLGAP1 p.His140Asp (c.418C>G) pathogenic?

DLGAP1 p.His140Asp (c.418C>G) is classified Uncertain significance in DLGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). AlphaMissense: likely pathogenic (0.9707); Ultra-rare (popmax 0.0217%, amr).

How common is DLGAP1 p.His140Asp (c.418C>G) in the general population?

DLGAP1 p.His140Asp (c.418C>G) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about DLGAP1 p.His140Asp (c.418C>G)?

AlphaMissense predicts likely pathogenic (score 0.9707) — an in-silico prediction, not a clinical call.

DLGAP1 p.His140Asp

c.418C>G · rs772003344 · VCV2314297

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9707 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9707	likely pathogenic · top 9% in DLGAP1
REVEL	0.679	pathogenic-leaning
SaProt	LLR -12.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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	29.9	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0217% Admixed American · 13/59,946 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00112% 18/1,605,634 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,611
Remaining individualsnot grpmax-eligible	0.00321%	31,192
European (non-Finnish)	0.000254%	393,091

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.His140Asp
Coding: c.418C>G
MANE Select: NM_004746
dbSNP: rs772003344
Type: single nucleotide variant
Location: chr18:3879651 (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-his140asp (accessed [today's date]).

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