Is NECTIN1 p.Trp14Cys (c.42G>C) pathogenic?

NECTIN1 p.Trp14Cys (c.42G>C) is classified Uncertain significance in NECTIN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-13). AlphaMissense: ambiguous (0.3608); Absent from gnomAD v4.1; Associated with cleft lip/palate-ectodermal dysplasia syndrome.

What condition is associated with NECTIN1 p.Trp14Cys (c.42G>C)?

NECTIN1 p.Trp14Cys (c.42G>C) is associated with cleft lip/palate-ectodermal dysplasia syndrome (ClinVar).

How common is NECTIN1 p.Trp14Cys (c.42G>C) in the general population?

NECTIN1 p.Trp14Cys (c.42G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NECTIN1 p.Trp14Cys (c.42G>C)?

AlphaMissense predicts ambiguous (score 0.3608) — an in-silico prediction, not a clinical call.

NECTIN1 p.Trp14Cys

c.42G>C · rs1591494857 · VCV878491

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3608 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,598,006)

Conditions

cleft lip/palate-ectodermal dysplasia syndrome

Computational evidence

Protein change
AlphaMissense	0.3608	ambiguous
REVEL	0.538	indeterminate
SaProt	LLR -7.65	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 0.97, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 64 kb · p 8.1e-06 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,598,006). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NECTIN1
Protein: p.Trp14Cys
Coding: c.42G>C
MANE Select: NM_002855
dbSNP: rs1591494857
Type: single nucleotide variant
Location: chr11:119728512 (GRCh38)
Gene constraint: LOEUF 0.659 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.80 · 6 PDB

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

Disease context

cleft lip/palate-ectodermal dysplasia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NECTIN1 c.*1139G>A Uncertain significance ★★ same condition
NECTIN1 c.*1179C>G Uncertain significance ★★ same condition
NECTIN1 c.*1595C>A Uncertain significance ★★ same condition
NECTIN1 c.*185T>C Uncertain significance ★★ same condition
NECTIN1 c.*2416A>G Uncertain significance ★★ same condition
NECTIN1 c.*3440G>A Uncertain significance ★★ same condition
NECTIN1 c.*3705G>A Uncertain significance ★★ same condition
NECTIN1 c.*607C>A Uncertain significance ★★ 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/nectin1-p-trp14cys (accessed [today's date]).

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