Is NECTIN2 p.Asp122= (c.366C>T) pathogenic?

NECTIN2 p.Asp122= (c.366C>T) is classified Benign in NECTIN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-31). Common (popmax 5.71%, afr) — too common for a highly-penetrant pathogenic allele.

NECTIN2 p.Asp122=

Q: How common is NECTIN2 p.Asp122= (c.366C>T) in the general population?

NECTIN2 p.Asp122= (c.366C>T) is common (popmax 5.71%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.366C>T · rs34929997 · VCV781489

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.71%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -14	GERP -3.7
Overall
CADD	0.323	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.71% African / African-American · 4,217/73,868 alleles

Filtering AF 5.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.51%

Overall 0.31% 4,863/1,569,090 alleles · common exomes 2,435/1,416,804 · genomes 2,428/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.71%	18
Remaining individualsnot grpmax-eligible	0.363%	276
Admixed American	0.266%	376
Middle Eastern	0.116%	860
European (non-Finnish)	0.0219%	4,561
South Asian	0.0208%	4,810
East Asian	0.00711%	14,073
Finnishnot grpmax-eligible	0.00173%	57,746

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: NECTIN2
Protein: p.Asp122=
Coding: c.366C>T
MANE Select: NM_001042724
dbSNP: rs34929997
Type: single nucleotide variant
Location: chr19:44865548 (GRCh38)
Gene constraint: LOEUF 0.658 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.78 · 8 PDB
Residue 122: the ig-like v-type domain

Full NECTIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NECTIN2 p.Arg286His Benign ★★ same type
NECTIN2 p.Glu401Gln Benign ★★ same type
NECTIN2 p.Arg43Ter Uncertain significance ★ same type
NECTIN2 p.Gly47Arg Uncertain significance ★ ⚠ same type
NECTIN2 p.Thr472Ile Uncertain significance ★ ⚠ same type
NECTIN2 p.Tyr454Cys Uncertain significance ★ ⚠ same type
NECTIN2 p.Val42Met Uncertain significance ★ same type
NECTIN2 c.1042+3795G>A Benign ★ 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/nectin2-p-asp122 (accessed [today's date]).

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