Is DLG5 p.Ala130Val (c.389C>T) pathogenic?

DLG5 p.Ala130Val (c.389C>T) is classified Likely benign in DLG5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-17). AlphaMissense: likely benign (0.092); Ultra-rare (popmax 0.025%, amr); Associated with DLG5-related disorder.

What condition is associated with DLG5 p.Ala130Val (c.389C>T)?

DLG5 p.Ala130Val (c.389C>T) is associated with DLG5-related disorder (ClinVar).

How common is DLG5 p.Ala130Val (c.389C>T) in the general population?

DLG5 p.Ala130Val (c.389C>T) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about DLG5 p.Ala130Val (c.389C>T)?

AlphaMissense predicts likely benign (score 0.092) — an in-silico prediction, not a clinical call.

DLG5 p.Ala130Val

c.389C>T · rs201454635 · VCV3054839

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.092 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DLG5-related disorder

Computational evidence

Protein change
AlphaMissense	0.092	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -7.18	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 5.8	phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 96 kb · p 1.7e-09 · regional, not allelic
Overall
CADD	23.8	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 0.025% Admixed American · 15/59,970 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.0163% 262/1,611,380 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.503%	199
Remaining individualsnot grpmax-eligible	0.0466%	2,148
Admixed Americangrpmax	0.025%	3,998
South Asian	0.00771%	12,965
European (non-Finnish)	0.005%	19,994
Finnishnot grpmax-eligible	0.00469%	21,333
African / African-American	0.00134%	74,830

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DLG5
Protein: p.Ala130Val
Coding: c.389C>T
MANE Select: NM_004747
dbSNP: rs201454635
Type: single nucleotide variant
Location: chr10:77856877 (GRCh38)
Gene constraint: LOEUF 0.333 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.25 · 1 PDB
Residue 130: the 'disordered' region

Full DLG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DLG5-related disorder

Similar variants

DLG5 p.Arg913Trp Uncertain significance ★ ⚠ same condition
DLG5 p.Glu1144Gly Uncertain significance ★ ⚠ same condition
DLG5 p.Gly994Asp Uncertain significance ★ ⚠ same condition
DLG5 p.Arg890His Likely benign same condition
DLG5 p.Val762Ile Likely benign ⚠ same condition
DLG5 p.Arg166Cys Uncertain significance ★★ ⚠ same type
DLG5 p.Leu1192Pro Uncertain significance ★★ ⚠ same type
DLG5 c.1622+8G>A Benign ★★ 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/dlg5-p-ala130val (accessed [today's date]).

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