Is DIP2A p.Pro798Leu (c.2393C>T) pathogenic?

DIP2A p.Pro798Leu (c.2393C>T) is classified Benign/Likely benign in DIP2A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-01). AlphaMissense: likely benign (0.1678); Low-frequency (popmax 1.31%, nfe).

How common is DIP2A p.Pro798Leu (c.2393C>T) in the general population?

DIP2A p.Pro798Leu (c.2393C>T) is low-frequency (popmax 1.31%, nfe) (gnomAD).

What do computational predictors say about DIP2A p.Pro798Leu (c.2393C>T)?

AlphaMissense predicts likely benign (score 0.1678) — an in-silico prediction, not a clinical call.

DIP2A p.Pro798Leu

c.2393C>T · rs144400668 · VCV775120

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1678 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.31%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1678	likely benign
REVEL	0.355	indeterminate
SaProt	LLR -9.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.8	GERP 0.77, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 108 kb · p 1.5e-11 · regional, not allelic
Overall
CADD	29.3	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 1.31% European (non-Finnish) · 15,468/1,179,896 alleles

Filtering AF 1.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.29%

Overall 1.04% 16,831/1,613,996 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.85%	35
European (non-Finnish)grpmax	1.31%	76
Remaining individualsnot grpmax-eligible	0.802%	125
South Asian	0.391%	256
Admixed American	0.348%	287
Middle Eastern	0.28%	357
Ashkenazi Jewishnot grpmax-eligible	0.199%	502
African / African-American	0.195%	514
Finnishnot grpmax-eligible	0.075%	1,333
East Asian	0.00223%	44,870

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro798Leu
Coding: c.2393C>T
MANE Select: NM_015151
dbSNP: rs144400668
Type: single nucleotide variant
Location: chr21:46545960 (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

Similar variants

DIP2A p.Ala676Thr Uncertain significance ★★ ⚠ same type
DIP2A p.Glu832Lys Uncertain significance ★★ ⚠ same type
DIP2A p.Pro333= Benign ★★ same type
DIP2A p.Thr848= Benign/Likely benign ★★ same type
DIP2A p.Val1531= Benign ★★ same type
DIP2A c.1429+2T>G Likely pathogenic ★ same type
DIP2A c.2395-2A>G Uncertain significance ★ same type
DIP2A p.Ala1017Thr 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/dip2a-p-pro798leu (accessed [today's date]).

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