Is DLGAP5 p.Ile23Ser (c.68T>G) pathogenic?

DLGAP5 p.Ile23Ser (c.68T>G) is classified Uncertain significance in DLGAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: ambiguous (0.445); Very rare (popmax 0.00381%, nfe).

How common is DLGAP5 p.Ile23Ser (c.68T>G) in the general population?

DLGAP5 p.Ile23Ser (c.68T>G) is very rare (popmax 0.00381%, nfe) (gnomAD).

What do computational predictors say about DLGAP5 p.Ile23Ser (c.68T>G)?

AlphaMissense predicts ambiguous (score 0.445) — an in-silico prediction, not a clinical call.

DLGAP5 p.Ile23Ser

c.68T>G · rs747869629 · VCV3082883

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.445 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00381%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.445	ambiguous
REVEL	0.142	moderately benign-leaning
SaProt	LLR -8.45	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 41 kb · p 0.094 · regional, not allelic
Overall
CADD	23.5	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 0.00381% European (non-Finnish) · 45/1,179,962 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00285% 46/1,613,846 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00381%	26,221
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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: DLGAP5
Protein: p.Ile23Ser
Coding: c.68T>G
MANE Select: NM_014750
dbSNP: rs747869629
Type: single nucleotide variant
Location: chr14:55189112 (GRCh38)
Gene constraint: LOEUF 1.112 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.52 · 4 PDB

Full DLGAP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLG1 p.His120Arg Uncertain significance ★★ ⚠ same type
DLG1 p.Ala262= Benign ★★ same type
DLG1 p.Asp633Glu Benign ★★ same type
DLG1 p.Ser470= Benign ★★ same type
DLG1 p.Val167= Benign ★★ same type
DLGAP5 c.1049+7A>C Benign ★★ same type
DLGAP5 c.2064-1G>A Likely pathogenic ★ same type
DLG1 c.484-11849C>T 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/dlgap5-p-ile23ser (accessed [today's date]).

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