Is DLGAP2 p.Ser85Cys (c.254C>G) pathogenic?

DLGAP2 p.Ser85Cys (c.254C>G) is classified Uncertain significance in DLGAP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely benign (0.1065); Very rare (popmax 0.000255%, nfe); Associated with DLGAP2-related disorder.

What condition is associated with DLGAP2 p.Ser85Cys (c.254C>G)?

DLGAP2 p.Ser85Cys (c.254C>G) is associated with DLGAP2-related disorder (ClinVar).

How common is DLGAP2 p.Ser85Cys (c.254C>G) in the general population?

DLGAP2 p.Ser85Cys (c.254C>G) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about DLGAP2 p.Ser85Cys (c.254C>G)?

AlphaMissense predicts likely benign (score 0.1065) — an in-silico prediction, not a clinical call.

DLGAP2 p.Ser85Cys

c.254C>G · VCV3353397

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1065 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DLGAP2-related disorder

Computational evidence

Protein change
AlphaMissense	0.1065	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -7.33	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	GERP 2.7, phastCons 0.75
Overall
CADD	23.4	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 S84C vs ClinVar S85C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000255% European (non-Finnish) · 3/1,178,216 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000187% 3/1,607,280 alleles · very rare

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: DLGAP2
Protein: p.Ser85Cys
Coding: c.254C>G
MANE Select: NM_001346810
Type: single nucleotide variant
Location: chr8:1548707 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 48.83
Residue 85: the 'disordered' region

Full DLGAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DLGAP2-related disorder

Similar variants

DLGAP2 p.Glu892Gln Uncertain significance ★ ⚠ same condition
DLGAP2 p.Asn662Thr Uncertain significance ⚠ same condition
DLGAP2 p.Leu192Val Uncertain significance ⚠ same condition
DLGAP2 c.107-10G>C Likely benign same condition
DLGAP2 c.1231-10C>G Likely benign same condition
DLGAP2 c.1810+10C>T Likely benign same condition
DLGAP2 c.2202+9C>T Likely benign same condition
DLGAP2 c.2949+5G>C Likely benign 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/dlgap2-p-ser85cys (accessed [today's date]).

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