Is DIAPH3 p.Ile320fs (c.958del) pathogenic?

DIAPH3 p.Ile320fs (c.958del) is classified Uncertain significance in DIAPH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). Very rare (popmax 0.00224%, eas).

How common is DIAPH3 p.Ile320fs (c.958del) in the general population?

DIAPH3 p.Ile320fs (c.958del) is very rare (popmax 0.00224%, eas) (gnomAD).

DIAPH3 p.Ile320fs

c.958del · rs755069320 · VCV1348803

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,584 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000623% 10/1,604,632 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,584
Remaining individualsnot grpmax-eligible	0.00161%	62,092
Finnishnot grpmax-eligible	0.00157%	63,678
African / African-American	0.00134%	74,526
South Asian	0.0011%	90,538
European (non-Finnish)	0.000426%	234,635

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.Ile320fs
Coding: c.958del
MANE Select: NM_001042517
dbSNP: rs755069320
Type: Deletion
Location: chr13:60008600 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.33 · 2 PDB
Residue 320: the gbd/fh3 domain

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

Similar variants

DIAPH3 p.Lys74fs Uncertain significance ★★ same type
DIAPH3 c.1651-17_1651-15del Likely benign ★★ same type
DIAPH3 c.3260-6del Benign/Likely benign ★★ same type
DIAPH3 c.1361+16_1361+31del Uncertain significance ★ same type
DIAPH3 p.Ala310fs Uncertain significance ★ same type
DIAPH3 p.Arg748del Uncertain significance ★ same type
DIAPH3 p.Gln1070fs Uncertain significance ★ same type
DIAPH3 p.Ile737fs 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-ile320fs (accessed [today's date]).

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