Is DLGAP2 p.Tyr120Phe (c.359A>T) pathogenic?

DLGAP2 p.Tyr120Phe (c.359A>T) is classified Uncertain significance in DLGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). AlphaMissense: likely benign (0.1233); Very rare (popmax 0.00345%, amr).

How common is DLGAP2 p.Tyr120Phe (c.359A>T) in the general population?

DLGAP2 p.Tyr120Phe (c.359A>T) is very rare (popmax 0.00345%, amr) (gnomAD).

What do computational predictors say about DLGAP2 p.Tyr120Phe (c.359A>T)?

AlphaMissense predicts likely benign (score 0.1233) — an in-silico prediction, not a clinical call.

DLGAP2 p.Tyr120Phe

c.359A>T · VCV3502397

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1233 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00345%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1233	likely benign
REVEL	0.338	indeterminate
SaProt	LLR -6.08	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 6.8	GERP 2.7, phastCons 1
Overall
CADD	22.4	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 Y119F vs ClinVar Y120F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00345% Admixed American · 2/57,928 alleles

Filtering AF 0.000573% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000214%

Overall 0.00014% 2/1,428,886 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.Tyr120Phe
Coding: c.359A>T
MANE Select: NM_001346810
Type: single nucleotide variant
Location: chr8:1548812 (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-tyr120phe (accessed [today's date]).

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