Is NECTIN1 p.Ser88= (c.264C>T) pathogenic?

NECTIN1 p.Ser88= (c.264C>T) is classified Conflicting classifications of pathogenicity in NECTIN1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-20). Low-frequency (popmax 2.11%, afr); Associated with cleft lip/palate-ectodermal dysplasia syndrome.

What condition is associated with NECTIN1 p.Ser88= (c.264C>T)?

NECTIN1 p.Ser88= (c.264C>T) is associated with cleft lip/palate-ectodermal dysplasia syndrome (ClinVar).

How common is NECTIN1 p.Ser88= (c.264C>T) in the general population?

NECTIN1 p.Ser88= (c.264C>T) is low-frequency (popmax 2.11%, afr) (gnomAD).

NECTIN1 p.Ser88=

c.264C>T · rs7131391 · VCV716975

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.11%, afr)

Conditions

cleft lip/palate-ectodermal dysplasia syndrome

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 -20	GERP -3.6
Overall
CADD	0.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.11% African / African-American · 1,584/75,024 alleles

Filtering AF 2.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.99%

Overall 0.272% 4,391/1,614,172 alleles · low-frequency exomes 3,290/1,461,874 · genomes 1,101/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.11%	47
Remaining individualsnot grpmax-eligible	0.339%	295
Admixed American	0.265%	378
South Asian	0.232%	432
Middle Eastern	0.215%	466
Finnishnot grpmax-eligible	0.184%	543
European (non-Finnish)	0.174%	574
Ashkenazi Jewishnot grpmax-eligible	0.125%	800
East Asian	0.00223%	44,884

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.Ser88=
Coding: c.264C>T
MANE Select: NM_002855
dbSNP: rs7131391
Type: single nucleotide variant
Location: chr11:119678581 (GRCh38)
Gene constraint: LOEUF 0.659 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.80 · 6 PDB
Residue 88: the ig-like v-type domain; a β-strand

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-ser88 (accessed [today's date]).

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