Is DIAPH3 p.Pro352= (c.1056T>C) pathogenic?

DIAPH3 p.Pro352= (c.1056T>C) is classified Likely benign in DIAPH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-02). Absent from gnomAD v4.1.

How common is DIAPH3 p.Pro352= (c.1056T>C) in the general population?

DIAPH3 p.Pro352= (c.1056T>C) is absent from gnomAD v4.1 (gnomAD).

DIAPH3 p.Pro352=

c.1056T>C · rs1594256733 · VCV753927

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -2.2, phastCons 1
Overall
CADD	9.012	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: DIAPH3
Protein: p.Pro352=
Coding: c.1056T>C
MANE Select: NM_001042517
dbSNP: rs1594256733
Type: single nucleotide variant
Location: chr13:59992542 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.33 · 2 PDB
Residue 352: the gbd/fh3 domain

Full DIAPH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIAPH3 p.Ala500Val Uncertain significance ★★ ⚠ same type
DIAPH3 p.Ala546Thr Uncertain significance ★★ ⚠ same type
DIAPH3 p.Arg1027His Uncertain significance ★★ ⚠ same type
DIAPH3 p.Arg1048Cys Uncertain significance ★★ ⚠ same type
DIAPH3 p.Arg1048Gly Uncertain significance ★★ ⚠ same type
DIAPH3 p.Arg1089Pro Uncertain significance ★★ ⚠ same type
DIAPH3 p.Arg1191Ter Uncertain significance ★★ same type
DIAPH3 p.Arg31Gln 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/diaph3-p-pro352 (accessed [today's date]).

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