Is DLG3 p.Arg114Pro (c.341G>C) pathogenic?

DLG3 p.Arg114Pro (c.341G>C) is classified Conflicting classifications of pathogenicity in DLG3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-01). AlphaMissense: likely pathogenic (0.712); Ultra-rare (popmax 0.012%, nfe); Associated with intellectual disability, X-linked 90.

What condition is associated with DLG3 p.Arg114Pro (c.341G>C)?

DLG3 p.Arg114Pro (c.341G>C) is associated with intellectual disability, X-linked 90 (ClinVar).

How common is DLG3 p.Arg114Pro (c.341G>C) in the general population?

DLG3 p.Arg114Pro (c.341G>C) is ultra-rare (popmax 0.012%, nfe) (gnomAD).

What do computational predictors say about DLG3 p.Arg114Pro (c.341G>C)?

AlphaMissense predicts likely pathogenic (score 0.712) — an in-silico prediction, not a clinical call.

DLG3 p.Arg114Pro

c.341G>C · rs759162614 · VCV931628

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.712 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability, X-linked 90

Computational evidence

Protein change
AlphaMissense	0.712	likely pathogenic
REVEL	0.371	indeterminate
SaProt	LLR -5.82	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 3,743 bp · p 0.36 · regional, not allelic
Overall
CADD	25.5	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

Grpmax group 0.012% European (non-Finnish) · 106/880,755 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00946%

Overall 0.00973% 115/1,181,364 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.012%	8,309
Remaining individualsnot grpmax-eligible	0.0107%	9,310
Ashkenazi Jewishnot grpmax-eligible	0.00466%	21,449
African / African-American	0.00352%	28,421
Finnishnot grpmax-eligible	0.00227%	43,971

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: DLG3
Protein: p.Arg114Pro
Coding: c.341G>C
MANE Select: NM_021120
dbSNP: rs759162614
Type: single nucleotide variant
Location: chrX:70445542 (GRCh38)
Structure: AlphaFold pLDDT 74.35 · 3 PDB

Full DLG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, X-linked 90 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLG3 p.Arg114= Likely benign ★ same residue
DLG3 p.Arg217Ter Pathogenic ★★ same condition
DLG3 p.Arg756Ter Pathogenic ★★ same condition
DLG3 p.Arg217Gln Uncertain significance ★★ ⚠ same condition
DLG3 p.Arg472His Uncertain significance ★★ ⚠ same condition
DLG3 p.Arg661Trp Uncertain significance ★★ ⚠ same condition
DLG3 p.Gly83Glu Uncertain significance ★★ ⚠ same condition
DLG3 p.His2Pro Uncertain significance ★★ ⚠ same condition

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/dlg3-p-arg114pro (accessed [today's date]).

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