Is EP400 p.Arg2377Ter (c.7129C>T) pathogenic?

EP400 p.Arg2377Ter (c.7129C>T) is classified Uncertain significance in EP400 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-01). Very rare (popmax 8.47e-05%, nfe).

How common is EP400 p.Arg2377Ter (c.7129C>T) in the general population?

EP400 p.Arg2377Ter (c.7129C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

EP400 p.Arg2377Ter

c.7129C>T · rs950154475 · VCV3026456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 39 of 53
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 3.8	GERP 1.4, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 6.84e-05% 1/1,461,874 alleles · very rare

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: EP400
Protein: p.Arg2377Ter
Coding: c.7129C>T
MANE Select: NM_015409
dbSNP: rs950154475
Type: single nucleotide variant
Location: chr12:132045829 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Residue 2377: an α-helix; the myb-like domain

Full EP400 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EP400 p.Arg2377Gln Uncertain significance ★ same residue
EP400 p.Thr664Ala Uncertain significance ★★ same type
EP400 c.1435+8G>A Benign ★★ same type
EP400 c.7027-9C>T Benign ★★ same type
EP400 p.Ala146= Likely benign ★★ same type
EP400 p.Ala1649Thr Benign/Likely benign ★★ same type
EP400 p.Ala1764= Benign ★★ same type
EP400 p.Ala244= Likely benign ★★ 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/ep400-p-arg2377ter (accessed [today's date]).

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