Is DIAPH3 p.Pro628= (c.1884A>G) pathogenic?

DIAPH3 p.Pro628= (c.1884A>G) is classified Likely benign in DIAPH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-13). Ultra-rare (popmax 0.0168%, mid).

How common is DIAPH3 p.Pro628= (c.1884A>G) in the general population?

DIAPH3 p.Pro628= (c.1884A>G) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

DIAPH3 p.Pro628=

c.1884A>G · rs1231532711 · VCV2191256

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

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 0.093	GERP -2.4, phastCons 0.32
Overall
CADD	6.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% Middle Eastern · 1/5,970 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000274% 4/1,461,682 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,970
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.000169%	589,984

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.Pro628=
Coding: c.1884A>G
MANE Select: NM_001042517
dbSNP: rs1231532711
Type: single nucleotide variant
Location: chr13:59970927 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.33 · 2 PDB
Residue 628: the fh1 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-pro628 (accessed [today's date]).

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