Is NECTIN2 p.Ser306= (c.918C>T) pathogenic?

NECTIN2 p.Ser306= (c.918C>T) is classified Likely benign in NECTIN2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-14). Ultra-rare (popmax 0.033%, mid); Associated with NECTIN2-related disorder.

What condition is associated with NECTIN2 p.Ser306= (c.918C>T)?

NECTIN2 p.Ser306= (c.918C>T) is associated with NECTIN2-related disorder (ClinVar).

How common is NECTIN2 p.Ser306= (c.918C>T) in the general population?

NECTIN2 p.Ser306= (c.918C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

NECTIN2 p.Ser306=

c.918C>T · rs139448288 · VCV3052752

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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 -13	GERP -4.6
Overall
CADD	0.216	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.0208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.00558% 90/1,614,146 alleles · ultra-rare exomes 86/1,461,846 · genomes 4/152,300 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
South Asian	0.0296%	3,374
Admixed American	0.00833%	12,002
Remaining individualsnot grpmax-eligible	0.0064%	15,627
European (non-Finnish)	0.00424%	23,600
African / African-American	0.00267%	37,522

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.Ser306=
Coding: c.918C>T
MANE Select: NM_001042724
dbSNP: rs139448288
Type: single nucleotide variant
Location: chr19:44874354 (GRCh38)
Gene constraint: LOEUF 0.658 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.78 · 8 PDB
Residue 306: the ig-like c2-type 2 domain

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-ser306 (accessed [today's date]).

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