Is NEBL p.Phe1012= (c.3036T>C) pathogenic?

NEBL p.Phe1012= (c.3036T>C) is classified Likely benign in NEBL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-03). Very rare (popmax 0.005%, amr); Associated with dilated cardiomyopathy.

What condition is associated with NEBL p.Phe1012= (c.3036T>C)?

NEBL p.Phe1012= (c.3036T>C) is associated with dilated cardiomyopathy (ClinVar).

How common is NEBL p.Phe1012= (c.3036T>C) in the general population?

NEBL p.Phe1012= (c.3036T>C) is very rare (popmax 0.005%, amr) (gnomAD).

NEBL p.Phe1012=

c.3036T>C · rs139338531 · VCV1965229

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.73 · evaluated, not missing
Pangolin	Δ0.24	gain · loss 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 0.94	GERP -2.9, phastCons 0.99
Overall
CADD	6.701	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,974 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00031% 5/1,613,684 alleles · very rare exomes 3/1,461,482 · genomes 2/152,202 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,991
African / African-American	0.00267%	37,457

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: NEBL
Protein: p.Phe1012=
Coding: c.3036T>C
MANE Select: NM_006393
dbSNP: rs139338531
Type: single nucleotide variant
Location: chr10:20785756 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB
Residue 1012: the sh3 domain; a β-strand

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

Disease context

dilated cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NEBL p.Phe1012Leu Uncertain significance ★ ⚠ same residue
NEBL c.1227+5G>A Uncertain significance ★★ same condition
NEBL c.1870-1G>A Uncertain significance ★★ same condition
NEBL c.798+1G>A Uncertain significance ★★ same condition
NEBL c.903+1G>T Uncertain significance ★★ same condition
NEBL p.Ala114Ser Uncertain significance ★★ ⚠ same condition
NEBL p.Ala219Thr Uncertain significance ★★ ⚠ same condition
NEBL p.Ala264Val 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/nebl-p-phe1012 (accessed [today's date]).

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