Is DIP2C p.Thr501Ser (c.1501A>T) pathogenic?

DIP2C p.Thr501Ser (c.1501A>T) is classified Uncertain significance in DIP2C (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-26). AlphaMissense: likely benign (0.2622); Absent from gnomAD v4.1; Associated with DIP2C-related disorder.

What condition is associated with DIP2C p.Thr501Ser (c.1501A>T)?

DIP2C p.Thr501Ser (c.1501A>T) is associated with DIP2C-related disorder (ClinVar).

How common is DIP2C p.Thr501Ser (c.1501A>T) in the general population?

DIP2C p.Thr501Ser (c.1501A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DIP2C p.Thr501Ser (c.1501A>T)?

AlphaMissense predicts likely benign (score 0.2622) — an in-silico prediction, not a clinical call.

DIP2C p.Thr501Ser

c.1501A>T · VCV3348237

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2622 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DIP2C-related disorder

Computational evidence

Protein change
AlphaMissense	0.2622	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -6.64	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 6.1	GERP 0.78, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 54 kb · p 2.7e-23 · regional, not allelic
Overall
CADD	21.9	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: DIP2C
Protein: p.Thr501Ser
Coding: c.1501A>T
MANE Select: NM_014974
Type: single nucleotide variant
Location: chr10:390087 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.64

Full DIP2C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DIP2C-related disorder

Similar variants

DIP2C p.Thr501= Likely benign ★ same residue
DIP2C p.Ser142Ala Uncertain significance ★★ ⚠ same condition
DIP2C c.2268+1G>A Likely pathogenic ★ same condition
DIP2C p.Arg1539Ter Conflicting classifications of pathogenicity ★ ⚠ same condition
DIP2C p.Arg77= Uncertain significance ★ same condition
DIP2C p.Val1440Ile Uncertain significance ★ ⚠ same condition
DIP2C p.Val1105Phe Uncertain significance ⚠ same condition
DIP2C c.1385-4C>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/dip2c-p-thr501ser (accessed [today's date]).

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