Is DIP2A p.Arg602Trp (c.1804C>T) pathogenic?

DIP2A p.Arg602Trp (c.1804C>T) is classified Uncertain significance in DIP2A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-03). AlphaMissense: likely benign (0.1934); Very rare (popmax 0.00411%, afr); Associated with DIP2A-related disorder.

What condition is associated with DIP2A p.Arg602Trp (c.1804C>T)?

DIP2A p.Arg602Trp (c.1804C>T) is associated with DIP2A-related disorder (ClinVar).

How common is DIP2A p.Arg602Trp (c.1804C>T) in the general population?

DIP2A p.Arg602Trp (c.1804C>T) is very rare (popmax 0.00411%, afr) (gnomAD).

What do computational predictors say about DIP2A p.Arg602Trp (c.1804C>T)?

AlphaMissense predicts likely benign (score 0.1934) — an in-silico prediction, not a clinical call.

DIP2A p.Arg602Trp

c.1804C>T · VCV3353263

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1934 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00411%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DIP2A-related disorder

Computational evidence

Protein change
AlphaMissense	0.1934	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -11.12	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.1	GERP -1.6, phastCons 0.001
Regional constraint	o/e 0.85	unconstrained · MANE · 108 kb · p 1.5e-11 · regional, not allelic
Overall
CADD	26.4	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

Grpmax group 0.00411% African / African-American · 3/73,034 alleles

Filtering AF 0.00109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000502%

Overall 0.000389% 6/1,544,170 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00411%	24,345
European (non-Finnish)	0.000261%	382,507

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: DIP2A
Protein: p.Arg602Trp
Coding: c.1804C>T
MANE Select: NM_015151
Type: single nucleotide variant
Location: chr21:46538485 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.93

Full DIP2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DIP2A-related disorder

Similar variants

DIP2A p.Arg602Gln Uncertain significance ★ ⚠ same residue
DIP2A p.Ala1026Ser Uncertain significance ★ ⚠ same condition
DIP2A c.2637+25G>T Uncertain significance same condition
DIP2A p.Ala1260Ser Uncertain significance ⚠ same condition
DIP2A p.Glu63Asp Uncertain significance ⚠ same condition
DIP2A p.Lys281Thr Uncertain significance ⚠ same condition
DIP2A p.Ser1249Cys Uncertain significance ⚠ same condition
DIP2A c.1707+7G>A 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/dip2a-p-arg602trp (accessed [today's date]).

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