Is DLGAP4 p.Val334Ala (c.1001T>C) pathogenic?

DLGAP4 p.Val334Ala (c.1001T>C) is classified Uncertain significance in DLGAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-17). AlphaMissense: ambiguous (0.5585); Very rare (popmax 0.00228%, eas).

How common is DLGAP4 p.Val334Ala (c.1001T>C) in the general population?

DLGAP4 p.Val334Ala (c.1001T>C) is very rare (popmax 0.00228%, eas) (gnomAD).

What do computational predictors say about DLGAP4 p.Val334Ala (c.1001T>C)?

AlphaMissense predicts ambiguous (score 0.5585) — an in-silico prediction, not a clinical call.

DLGAP4 p.Val334Ala

c.1001T>C · rs2517652719 · VCV2267910

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5585 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00228%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5585	ambiguous
REVEL	0.647	pathogenic-leaning
SaProt	LLR -5.90	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 95 kb · p 8.8e-13 · regional, not allelic
Overall
CADD	24.3	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 0.00228% East Asian · 1/43,916 alleles

Overall 7.06e-05% 1/1,415,458 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: DLGAP4
Protein: p.Val334Ala
Coding: c.1001T>C
MANE Select: NM_001365621
dbSNP: rs2517652719
Type: single nucleotide variant
Location: chr20:36436110 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.01

Full DLGAP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLGAP4 p.Pro572Leu Uncertain significance ★★ ⚠ same type
DLGAP4 p.Ala845= Benign ★★ same type
DLGAP4 p.Gly540Ser Likely benign ★★ same type
DLGAP4 p.Pro270= Likely benign ★★ same type
DLGAP4 c.2011-343A>T Uncertain significance ★ same type
DLGAP4 p.Ala131Thr Uncertain significance ★ ⚠ same type
DLGAP4 p.Ala154Pro Uncertain significance ★ ⚠ same type
DLGAP4 p.Ala154Ser 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/dlgap4-p-val334ala (accessed [today's date]).

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