Is DIP2B p.Ala1208Ser (c.3622G>T) pathogenic?

DIP2B p.Ala1208Ser (c.3622G>T) is classified Uncertain significance in DIP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-16). AlphaMissense: likely benign (0.0936); Absent from gnomAD v4.1; Associated with DIP2B-related disorder.

What condition is associated with DIP2B p.Ala1208Ser (c.3622G>T)?

DIP2B p.Ala1208Ser (c.3622G>T) is associated with DIP2B-related disorder (ClinVar).

How common is DIP2B p.Ala1208Ser (c.3622G>T) in the general population?

DIP2B p.Ala1208Ser (c.3622G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DIP2B p.Ala1208Ser (c.3622G>T)?

AlphaMissense predicts likely benign (score 0.0936) — an in-silico prediction, not a clinical call.

DIP2B p.Ala1208Ser

c.3622G>T · rs753667447 · VCV2633697

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0936 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DIP2B-related disorder

Computational evidence

Protein change
AlphaMissense	0.0936	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -7.12	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 9.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 240 kb · p 4.2e-21 · regional, not allelic
Overall
CADD	24.4	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DIP2B
Protein: p.Ala1208Ser
Coding: c.3622G>T
MANE Select: NM_173602
dbSNP: rs753667447
Type: single nucleotide variant
Location: chr12:50728659 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.83

Full DIP2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DIP2B-related disorder

Similar variants

DIP2B p.Ala1101Asp Uncertain significance ★ same condition
DIP2B p.Glu172Ala Uncertain significance ★ ⚠ same condition
DIP2B p.Thr1016Asn Uncertain significance ★ ⚠ same condition
DIP2B p.Ala897Pro Uncertain significance ⚠ same condition
DIP2B p.Asp1565Gly Uncertain significance ⚠ same condition
DIP2B p.Ile792Val Conflicting classifications of pathogenicity ⚠ same condition
DIP2B p.Thr746Arg Uncertain significance ⚠ same condition
DIP2B c.1654+10C>T 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/dip2b-p-ala1208ser (accessed [today's date]).

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