Is NECTIN1 p.Asp46= (c.138C>T) pathogenic?

NECTIN1 p.Asp46= (c.138C>T) is classified Likely benign in NECTIN1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-05). Very rare (popmax 0.00329%, sas); Associated with NECTIN1-related disorder.

What condition is associated with NECTIN1 p.Asp46= (c.138C>T)?

NECTIN1 p.Asp46= (c.138C>T) is associated with NECTIN1-related disorder (ClinVar).

How common is NECTIN1 p.Asp46= (c.138C>T) in the general population?

NECTIN1 p.Asp46= (c.138C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

NECTIN1 p.Asp46=

c.138C>T · rs111847127 · VCV3052918

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

NECTIN1-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 -3.7	GERP -3.6
Overall
CADD	4.044	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,050 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00136% 22/1,613,860 alleles · very rare exomes 22/1,461,644 · genomes 0/152,216 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,350
Remaining individualsnot grpmax-eligible	0.0016%	62,506
Finnishnot grpmax-eligible	0.00156%	63,910
European (non-Finnish)	0.00136%	73,747
African / African-American	0.00133%	75,010

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.Asp46=
Coding: c.138C>T
MANE Select: NM_002855
dbSNP: rs111847127
Type: single nucleotide variant
Location: chr11:119678707 (GRCh38)
Gene constraint: LOEUF 0.659 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.80 · 6 PDB
Residue 46: the ig-like v-type domain

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

Disease context

NECTIN1-related disorder

Similar variants

NECTIN1 c.1003+534G>A Likely benign same condition
NECTIN1 c.1003+557G>T Benign same condition
NECTIN1 c.79+9G>A Likely benign same condition
NECTIN1 p.Ala351= Likely benign same condition
NECTIN1 p.Gln409= Likely benign same condition
NECTIN1 p.Pro340= Likely benign same condition
NECTIN1 p.Thr21= Likely benign same condition
NECTIN1 c.*1139G>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-asp46 (accessed [today's date]).

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