Is DLG4 p.Pro154= (c.462G>A) pathogenic?

DLG4 p.Pro154= (c.462G>A) is classified Likely benign in DLG4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-01). Rare (popmax 0.297%, mid).

How common is DLG4 p.Pro154= (c.462G>A) in the general population?

DLG4 p.Pro154= (c.462G>A) is rare (popmax 0.297%, mid) (gnomAD).

DLG4 p.Pro154=

c.462G>A · rs201426589 · VCV2647320

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.297%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4.8
Overall
CADD	0.376	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.297% Middle Eastern · 18/6,056 alleles

Filtering AF 0.192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.159%

Overall 0.0651% 1,050/1,612,532 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.872%	115
Middle Easterngrpmax	0.297%	336
Remaining individualsnot grpmax-eligible	0.154%	650
Admixed American	0.145%	690
African / African-American	0.06%	1,667
European (non-Finnish)	0.0452%	2,211
East Asian	0.00893%	11,201
Finnishnot grpmax-eligible	0.00782%	12,792
South Asian	0.00439%	22,760

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: DLG4
Protein: p.Pro154=
Coding: c.462G>A
MANE Select: NM_001321075
dbSNP: rs201426589
Type: single nucleotide variant
Location: chr17:7203467 (GRCh38)
Gene constraint: LOEUF 0.151 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.00 · 24 PDB
Residue 154: an α-helix

Full DLG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLG4 c.1084-1G>T Pathogenic/Likely pathogenic ★★ same type
DLG4 c.1478+2T>C Pathogenic/Likely pathogenic ★★ same type
DLG4 c.1543+2T>C Pathogenic/Likely pathogenic ★★ same type
DLG4 c.1592-1G>A Pathogenic/Likely pathogenic ★★ same type
DLG4 c.1693+1G>A Pathogenic/Likely pathogenic ★★ same type
DLG4 c.1866+2T>C Pathogenic/Likely pathogenic ★★ same type
DLG4 c.210+1G>T Likely pathogenic ★★ same type
DLG4 c.211-2A>G Pathogenic/Likely pathogenic ★★ 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/dlg4-p-pro154 (accessed [today's date]).

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