Is NECTIN1 p.Phe53= (c.159T>C) pathogenic?

NECTIN1 p.Phe53= (c.159T>C) is classified Likely benign in NECTIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-20). Very rare (popmax 0.00254%, nfe).

How common is NECTIN1 p.Phe53= (c.159T>C) in the general population?

NECTIN1 p.Phe53= (c.159T>C) is very rare (popmax 0.00254%, nfe) (gnomAD).

NECTIN1 p.Phe53=

c.159T>C · VCV3605106

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -3.6
Overall
CADD	6.359	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00254% European (non-Finnish) · 30/1,179,996 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00192% 31/1,613,852 alleles · very rare exomes 30/1,461,802 · genomes 1/152,050 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00254%	39,333
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Phe53=
Coding: c.159T>C
MANE Select: NM_002855
Type: single nucleotide variant
Location: chr11:119678686 (GRCh38)
Gene constraint: LOEUF 0.659 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.80 · 6 PDB
Residue 53: the ig-like v-type domain

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

Similar variants

NECTIN1 c.*1139G>A Uncertain significance ★★ same type
NECTIN1 c.*1179C>G Uncertain significance ★★ same type
NECTIN1 c.*1595C>A Uncertain significance ★★ same type
NECTIN1 c.*185T>C Uncertain significance ★★ same type
NECTIN1 c.*2416A>G Uncertain significance ★★ same type
NECTIN1 c.*3440G>A Uncertain significance ★★ same type
NECTIN1 c.*3705G>A Uncertain significance ★★ same type
NECTIN1 c.*607C>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-phe53 (accessed [today's date]).

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