Is NECTIN1 p.Arg382= (c.1146G>A) pathogenic?

NECTIN1 p.Arg382= (c.1146G>A) is classified Likely benign in NECTIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-17). Very rare (popmax 0.00653%, nfe).

How common is NECTIN1 p.Arg382= (c.1146G>A) in the general population?

NECTIN1 p.Arg382= (c.1146G>A) is very rare (popmax 0.00653%, nfe) (gnomAD).

NECTIN1 p.Arg382=

c.1146G>A · VCV3603798

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00653%, 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 -0.43
Overall
CADD	4.203	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00653% European (non-Finnish) · 77/1,179,892 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0049%

Overall 0.00477% 77/1,613,072 alleles · very rare exomes 75/1,460,954 · genomes 2/152,118 · joint denominator

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: NECTIN1
Protein: p.Arg382=
Coding: c.1146G>A
MANE Select: NM_002855
Type: single nucleotide variant
Location: chr11:119665155 (GRCh38)
Gene constraint: LOEUF 0.659 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.80 · 6 PDB
Residue 382: a UniProt-annotated variant site (in edmi); a UniProt-annotated variant site (in edmi and ofc7)

Full NECTIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NECTIN1 c.*1139G>A Uncertain significance ★★ same type
NECTIN1 c.*1179C>G Uncertain significance ★★ same type
NECTIN1 c.*1595C>A Uncertain significance ★★ same type
NECTIN1 c.*185T>C Uncertain significance ★★ same type
NECTIN1 c.*2416A>G Uncertain significance ★★ same type
NECTIN1 c.*3440G>A Uncertain significance ★★ same type
NECTIN1 c.*3705G>A Uncertain significance ★★ same type
NECTIN1 c.*607C>A 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/nectin1-p-arg382 (accessed [today's date]).

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