Is DLGAP2 p.Ala534Val (c.1601C>T) pathogenic?

DLGAP2 p.Ala534Val (c.1601C>T) is classified Uncertain significance in DLGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). AlphaMissense: likely benign (0.108); Ultra-rare (popmax 0.0267%, afr).

How common is DLGAP2 p.Ala534Val (c.1601C>T) in the general population?

DLGAP2 p.Ala534Val (c.1601C>T) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

What do computational predictors say about DLGAP2 p.Ala534Val (c.1601C>T)?

AlphaMissense predicts likely benign (score 0.108) — an in-silico prediction, not a clinical call.

DLGAP2 p.Ala534Val

c.1601C>T · VCV3502377

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.108 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.108	likely benign
REVEL	0.456	indeterminate
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 0.18, phastCons 1
Overall
CADD	22.3	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 A533V vs ClinVar A534V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% African / African-American · 20/74,960 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00305% 49/1,608,698 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,748
Middle Eastern	0.0166%	6,026
East Asian	0.0112%	8,960
South Asian	0.00222%	45,069
Admixed American	0.00167%	59,758
European (non-Finnish)	0.00161%	61,936
Remaining individualsnot grpmax-eligible	0.00161%	62,292

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.Ala534Val
Coding: c.1601C>T
MANE Select: NM_001346810
Type: single nucleotide variant
Location: chr8:1632837 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 48.83

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

Similar variants

DLGAP2 c.1810+14A>G Benign ★★ same type
DLGAP2 c.2160+19C>G Benign ★★ same type
DLGAP2 p.Glu678= Benign ★★ same type
DLGAP2 p.Pro464Gln Benign ★★ same type
DLGAP2 c.2203-7G>T Uncertain significance ★ same type
DLGAP2 p.Ala1019Gly Uncertain significance ★ ⚠ same type
DLGAP2 p.Ala1026Val Uncertain significance ★ same type
DLGAP2 p.Ala116Thr 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/dlgap2-p-ala534val (accessed [today's date]).

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