Is DIP2B p.Ser80Tyr (c.239C>A) pathogenic?

DIP2B p.Ser80Tyr (c.239C>A) is classified Uncertain significance in DIP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). AlphaMissense: likely benign (0.1434); Very rare (popmax 0.0011%, sas).

How common is DIP2B p.Ser80Tyr (c.239C>A) in the general population?

DIP2B p.Ser80Tyr (c.239C>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DIP2B p.Ser80Tyr (c.239C>A)?

AlphaMissense predicts likely benign (score 0.1434) — an in-silico prediction, not a clinical call.

DIP2B p.Ser80Tyr

c.239C>A · rs771056180 · VCV2556344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1434 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1434	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -10.16	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 240 kb · p 4.2e-21 · regional, not allelic
Overall
CADD	21.7	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 0.0011% South Asian · 1/91,078 alleles

Overall 6.84e-05% 1/1,461,744 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: DIP2B
Protein: p.Ser80Tyr
Coding: c.239C>A
MANE Select: NM_173602
dbSNP: rs771056180
Type: single nucleotide variant
Location: chr12:50640790 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.83
Residue 80: the dmap1-binding domain; the 'disordered' region

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-ser80tyr (accessed [today's date]).

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