Is PDZD7 p.Lys892del (c.2672AGA[1]) pathogenic?

PDZD7 p.Lys892del (c.2672AGA[1]) is classified Conflicting classifications of pathogenicity in PDZD7 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-03-04). Very rare (popmax 0.00506%, nfe); Associated with PDZD7-related disorder.

What condition is associated with PDZD7 p.Lys892del (c.2672AGA[1])?

PDZD7 p.Lys892del (c.2672AGA[1]) is associated with PDZD7-related disorder, hearing loss disorder, hearing loss, autosomal recessive 57 (ClinVar).

How common is PDZD7 p.Lys892del (c.2672AGA[1]) in the general population?

PDZD7 p.Lys892del (c.2672AGA[1]) is very rare (popmax 0.00506%, nfe) (gnomAD).

PDZD7 p.Lys892del

c.2672AGA[1] · rs397516636 · VCV44131

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00506%, nfe)

Conditions

PDZD7-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00506% European (non-Finnish) · 58/1,146,842 alleles

Filtering AF 0.00397% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00363%

Overall 0.00391% 60/1,535,908 alleles · very rare exomes 59/1,383,734 · genomes 1/152,174 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00506%	19,773
Remaining individualsnot grpmax-eligible	0.00167%	59,994
African / African-American	0.00137%	73,014

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: PDZD7
Protein: p.Lys892del
Coding: c.2672AGA[1]
MANE Select: NM_001195263
dbSNP: rs397516636
Type: Microsatellite
Location: chr10:101009291 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.10 · 2 PDB
Residue 892: a UniProt-annotated variant site (in dfnb57); the pdz 3 domain; a β-strand

Full PDZD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PDZD7-related disorder

Also linked: hearing loss disorder hearing loss, autosomal recessive 57

Similar variants

PDZD7 p.773RS[7] Benign ★★ same condition
PDZD7 p.Glu487fs Likely pathogenic ★ same condition
PDZD7 c.2005+6_2005+9del Uncertain significance ★ same condition
PDZD7 p.Lys892Thr Uncertain significance ★ ⚠ same residue
PDZD7 c.1749+2T>G Likely pathogenic ★★ same condition
PDZD7 c.1750-2A>G Likely pathogenic ★★ same condition
PDZD7 c.1933+1G>A Pathogenic/Likely pathogenic ★★ same condition
PDZD7 c.928+1G>A Likely pathogenic ★★ same condition

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/pdzd7-p-lys892del (accessed [today's date]).

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