Is NEBL p.Pro208= (c.624C>T) pathogenic?

NEBL p.Pro208= (c.624C>T) is classified Benign/Likely benign in NEBL (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-27). Rare (popmax 0.365%, afr); Associated with dilated cardiomyopathy.

What condition is associated with NEBL p.Pro208= (c.624C>T)?

NEBL p.Pro208= (c.624C>T) is associated with dilated cardiomyopathy (ClinVar).

How common is NEBL p.Pro208= (c.624C>T) in the general population?

NEBL p.Pro208= (c.624C>T) is rare (popmax 0.365%, afr) (gnomAD).

NEBL p.Pro208=

c.624C>T · rs111854914 · VCV164761

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.365%, afr)

Conditions

dilated cardiomyopathy

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 -1.2	GERP -5
Overall
CADD	9.123	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.365% African / African-American · 273/74,872 alleles

Filtering AF 0.329% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.315%

Overall 0.02% 323/1,612,428 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.365%	274
Remaining individualsnot grpmax-eligible	0.0208%	4,804
Admixed American	0.015%	6,663
South Asian	0.00439%	22,761
European (non-Finnish)	0.00204%	49,119

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.Pro208=
Coding: c.624C>T
MANE Select: NM_006393
dbSNP: rs111854914
Type: single nucleotide variant
Location: chr10:20868724 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB

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.Pro208Ala 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-pro208 (accessed [today's date]).

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