Is DLG2 p.Pro471Ser (c.1411C>T) pathogenic?

DLG2 p.Pro471Ser (c.1411C>T) is classified Uncertain significance in DLG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.149); Ultra-rare (popmax 0.0133%, amr).

How common is DLG2 p.Pro471Ser (c.1411C>T) in the general population?

DLG2 p.Pro471Ser (c.1411C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about DLG2 p.Pro471Ser (c.1411C>T)?

AlphaMissense predicts likely benign (score 0.149) — an in-silico prediction, not a clinical call.

DLG2 p.Pro471Ser

c.1411C>T · rs181668459 · VCV2368107

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.149 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.149	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -6.95	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	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 147 kb · p 0.76 · regional, not allelic
Overall
CADD	26.8	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P366S vs ClinVar P471S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/60,016 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.000867% 14/1,614,064 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,502
Remaining individualsnot grpmax-eligible	0.0064%	15,625
African / African-American	0.00267%	37,515

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: DLG2
Protein: p.Pro471Ser
Coding: c.1411C>T
MANE Select: NM_001142699
dbSNP: rs181668459
Type: single nucleotide variant
Location: chr11:83930413 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 69.93 · 2 PDB
Residue 471: the pdz 3 domain

Full DLG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLG2 p.Arg797= Benign ★★ same type
DLG2 p.Gln944= Benign ★★ same type
DLG2 p.Leu459= Benign ★★ same type
DLG2 p.Leu514Pro Likely benign ★★ same type
DLG2 p.Lys59= Benign ★★ same type
DLG2 p.Ser804= Benign/Likely benign ★★ same type
DLG2 c.624+1G>A Uncertain significance ★ same type
DLG2 p.Ala128Pro 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/dlg2-p-pro471ser (accessed [today's date]).

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