Is DIAPH3 p.Arg1129= (c.3387G>A) pathogenic?

DIAPH3 p.Arg1129= (c.3387G>A) is classified Likely benign in DIAPH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-29). Very rare (popmax 0.00178%, nfe).

How common is DIAPH3 p.Arg1129= (c.3387G>A) in the general population?

DIAPH3 p.Arg1129= (c.3387G>A) is very rare (popmax 0.00178%, nfe) (gnomAD).

DIAPH3 p.Arg1129=

c.3387G>A · rs370662741 · VCV2905692

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

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 2.3	GERP 0.89, phastCons 1
Overall
CADD	9.579	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,180,002 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0013% 21/1,614,074 alleles · very rare

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: DIAPH3
Protein: p.Arg1129=
Coding: c.3387G>A
MANE Select: NM_001042517
dbSNP: rs370662741
Type: single nucleotide variant
Location: chr13:59666779 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.33 · 2 PDB

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

Similar variants

DIAPH3 p.Arg1129Lys Uncertain significance ★ ⚠ same residue
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

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-arg1129 (accessed [today's date]).

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