Is DIP2B p.Ser376Arg (c.1128C>G) pathogenic?

DIP2B p.Ser376Arg (c.1128C>G) is classified Uncertain significance in DIP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-03). AlphaMissense: likely pathogenic (0.9744); Absent from gnomAD v4.1.

How common is DIP2B p.Ser376Arg (c.1128C>G) in the general population?

DIP2B p.Ser376Arg (c.1128C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DIP2B p.Ser376Arg (c.1128C>G)?

AlphaMissense predicts likely pathogenic (score 0.9744) — an in-silico prediction, not a clinical call.

DIP2B p.Ser376Arg

c.1128C>G · VCV4840906

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9744 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9744	likely pathogenic
REVEL	0.247	benign-leaning
SaProt	LLR -12.44	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -0.08, 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

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.Ser376Arg
Coding: c.1128C>G
MANE Select: NM_173602
Type: single nucleotide variant
Location: chr12:50680685 (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

Similar variants

DIP2B p.Asp501Val Uncertain significance ★★ ⚠ same type
DIP2B p.Cys1071Ser Uncertain significance ★★ ⚠ same type
DIP2B p.His1027Arg Uncertain significance ★★ ⚠ same type
DIP2B p.Ile681Val Uncertain significance ★★ ⚠ same type
DIP2B p.Ile968Thr Uncertain significance ★★ ⚠ same type
DIP2B p.Ile994Leu Uncertain significance ★★ ⚠ same type
DIP2B p.Pro244Ala Uncertain significance ★★ ⚠ same type
DIP2B p.Pro513Ser 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/dip2b-p-ser376arg (accessed [today's date]).

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