Is PACS2 p.Arg796= (c.2386C>A) pathogenic?

PACS2 p.Arg796= (c.2386C>A) is classified Uncertain significance in PACS2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-26). Absent from gnomAD v4.1.

How common is PACS2 p.Arg796= (c.2386C>A) in the general population?

PACS2 p.Arg796= (c.2386C>A) is absent from gnomAD v4.1 (gnomAD).

PACS2 p.Arg796=

c.2386C>A · rs1595193008 · VCV1684981

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.71	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

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: PACS2
Protein: p.Arg796=
Coding: c.2386C>A
MANE Select: NM_001100913
dbSNP: rs1595193008
Type: single nucleotide variant
Location: chr14:105392749 (GRCh38)
Gene constraint: LOEUF 0.561 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.10

Full PACS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PACS2 p.Arg796Gln Uncertain significance ★ ⚠ same residue
PACS2 p.Arg796Trp Uncertain significance ★ ⚠ same residue
PACS2 p.Glu209Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
PACS2 c.1413+2T>C Uncertain significance ★★ same type
PACS2 p.Ala526Val Uncertain significance ★★ ⚠ same type
PACS2 p.Ala704Thr Uncertain significance ★★ ⚠ same type
PACS2 p.Ala883Thr Uncertain significance ★★ ⚠ same type
PACS2 p.Arg431Gln 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/pacs2-p-arg796 (accessed [today's date]).

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