Is NECTIN4 p.Pro304fs (c.906del) pathogenic?

NECTIN4 p.Pro304fs (c.906del) is classified Pathogenic in NECTIN4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2010-08-13). Absent from gnomAD; Associated with ectodermal dysplasia-syndactyly syndrome 1.

What condition is associated with NECTIN4 p.Pro304fs (c.906del)?

NECTIN4 p.Pro304fs (c.906del) is associated with ectodermal dysplasia-syndactyly syndrome 1 (ClinVar).

How common is NECTIN4 p.Pro304fs (c.906del) in the general population?

NECTIN4 p.Pro304fs (c.906del) is absent from gnomAD (gnomAD).

NECTIN4 p.Pro304fs

c.906del · rs730880260 · VCV1602

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ectodermal dysplasia-syndactyly syndrome 1

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 5 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NECTIN4
Protein: p.Pro304fs
Coding: c.906del
MANE Select: NM_030916
dbSNP: rs730880260
Type: Deletion
Location: chr1:161074705 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 79.79 · 5 PDB
Residue 304: a disulfide bond; the ig-like c2-type 2 domain

Full NECTIN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ectodermal dysplasia-syndactyly syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NECTIN4 p.Pro463Ala Uncertain significance ★★ ⚠ same condition
NECTIN4 p.Thr497Met Uncertain significance ★★ ⚠ same condition
NECTIN4 p.Arg294Ter Pathogenic ★ same condition
NECTIN4 p.Arg506Trp Likely pathogenic ★ same condition
NECTIN4 p.Gln77Ter Pathogenic ★ same condition
NECTIN4 p.Arg443Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
NECTIN4 p.Arg493Pro Uncertain significance ★ ⚠ same condition
NECTIN4 p.Tyr125Ser Uncertain significance ★ ⚠ 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/nectin4-p-pro304fs (accessed [today's date]).

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