Is EPAS1 p.Ser413= (c.1239T>A) pathogenic?

EPAS1 p.Ser413= (c.1239T>A) is classified Likely benign in EPAS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-06). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EPAS1 p.Ser413= (c.1239T>A)?

EPAS1 p.Ser413= (c.1239T>A) is associated with Inborn genetic diseases (ClinVar).

How common is EPAS1 p.Ser413= (c.1239T>A) in the general population?

EPAS1 p.Ser413= (c.1239T>A) is absent from gnomAD v4.1 (gnomAD).

EPAS1 p.Ser413=

c.1239T>A · rs2546471769 · VCV1757726

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

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 0.33	GERP -0.46, phastCons 1
Overall
CADD	7.835	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EPAS1
Protein: p.Ser413=
Coding: c.1239T>A
MANE Select: NM_001430
dbSNP: rs2546471769
Type: single nucleotide variant
Location: chr2:46376743 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.41 · 43 PDB

Full EPAS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EPAS1 p.Ser413Cys Uncertain significance ★ ⚠ same residue
EPAS1 p.Ser413Phe Uncertain significance ★ ⚠ same residue
EPAS1 p.Ala439Gly Uncertain significance ★★ ⚠ same condition
EPAS1 p.Ala463Thr Uncertain significance ★★ ⚠ same condition
EPAS1 p.Ala698Pro Uncertain significance ★★ ⚠ same condition
EPAS1 p.Ala758Thr Uncertain significance ★★ ⚠ same condition
EPAS1 p.Ala81Thr Uncertain significance ★★ ⚠ same condition
EPAS1 p.Ala83Asp 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/epas1-p-ser413 (accessed [today's date]).

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