Is DLGAP4 p.Arg712Trp (c.2134C>T) pathogenic?

DLGAP4 p.Arg712Trp (c.2134C>T) is classified Uncertain significance in DLGAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely benign (0.113); Ultra-rare (popmax 0.014%, amr).

How common is DLGAP4 p.Arg712Trp (c.2134C>T) in the general population?

DLGAP4 p.Arg712Trp (c.2134C>T) is ultra-rare (popmax 0.014%, amr) (gnomAD).

What do computational predictors say about DLGAP4 p.Arg712Trp (c.2134C>T)?

AlphaMissense predicts likely benign (score 0.113) — an in-silico prediction, not a clinical call.

DLGAP4 p.Arg712Trp

c.2134C>T · VCV3502406

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.113 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.014%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.113	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -7.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.46 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 95 kb · p 8.8e-13 · regional, not allelic
Overall
CADD	28.2	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 0.014% Admixed American · 8/57,292 alleles

Filtering AF 0.00688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00502%

Overall 0.00157% 25/1,596,334 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.014%	7,161
Remaining individualsnot grpmax-eligible	0.00486%	20,573
East Asian	0.00455%	22,000
African / African-American	0.00135%	74,272
South Asian	0.00113%	88,424
European (non-Finnish)	0.000854%	117,136

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: DLGAP4
Protein: p.Arg712Trp
Coding: c.2134C>T
MANE Select: NM_001365621
Type: single nucleotide variant
Location: chr20:36500233 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.01
Residue 712: 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-arg712trp (accessed [today's date]).

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