Is NECTIN2 p.Ser430= (c.1290G>A) pathogenic?

NECTIN2 p.Ser430= (c.1290G>A) is classified Likely benign in NECTIN2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-05-19). Ultra-rare (popmax 0.0147%, afr); Associated with NECTIN2-related disorder.

What condition is associated with NECTIN2 p.Ser430= (c.1290G>A)?

NECTIN2 p.Ser430= (c.1290G>A) is associated with NECTIN2-related disorder (ClinVar).

How common is NECTIN2 p.Ser430= (c.1290G>A) in the general population?

NECTIN2 p.Ser430= (c.1290G>A) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

NECTIN2 p.Ser430=

c.1290G>A · rs376996543 · VCV3048558

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Conditions

NECTIN2-related disorder

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 -2.1	GERP -4.5
Overall
CADD	1.801	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,868 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.00335% 54/1,613,008 alleles · ultra-rare exomes 45/1,460,910 · genomes 9/152,098 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,806
Remaining individualsnot grpmax-eligible	0.0128%	7,800
Admixed American	0.0117%	8,568
European (non-Finnish)	0.00229%	43,698
South Asian	0.0011%	91,036

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.Ser430=
Coding: c.1290G>A
MANE Select: NM_001042724
dbSNP: rs376996543
Type: single nucleotide variant
Location: chr19:44886162 (GRCh38)
Gene constraint: LOEUF 0.658 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.78 · 8 PDB

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

Disease context

NECTIN2-related disorder

Similar variants

NECTIN2 p.Tyr454Cys Uncertain significance ★ ⚠ same condition
NECTIN2 p.Thr390Met Uncertain significance ⚠ same condition
NECTIN2 c.1042+3797G>T Likely benign same condition
NECTIN2 c.1043-3861G>A Likely benign same condition
NECTIN2 c.1261-9C>T Benign same condition
NECTIN2 c.89-10C>T Likely benign same condition
NECTIN2 p.Ala214= Likely benign same condition
NECTIN2 p.Arg222Cys Likely benign ⚠ 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/nectin2-p-ser430 (accessed [today's date]).

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