Is EPAS1 p.Ser814= (c.2442G>A) pathogenic?

EPAS1 p.Ser814= (c.2442G>A) is classified Benign/Likely benign in EPAS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-13). Rare (popmax 0.109%, afr); Associated with Inborn genetic diseases.

What condition is associated with EPAS1 p.Ser814= (c.2442G>A)?

EPAS1 p.Ser814= (c.2442G>A) is associated with Inborn genetic diseases, erythrocytosis, familial, 4 (ClinVar).

How common is EPAS1 p.Ser814= (c.2442G>A) in the general population?

EPAS1 p.Ser814= (c.2442G>A) is rare (popmax 0.109%, afr) (gnomAD).

EPAS1 p.Ser814=

c.2442G>A · rs4953362 · VCV1791348

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.109%, afr)

Conditions

Inborn genetic diseases

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 -7.5	GERP -3.5
Overall
CADD	0.047	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.109% African / African-American · 82/75,050 alleles

Filtering AF 0.0902% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0831%

Overall 0.0088% 142/1,614,116 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.109%	915
Middle Eastern	0.033%	3,031
South Asian	0.0143%	7,007
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Finnishnot grpmax-eligible	0.00625%	15,988
Admixed American	0.00333%	30,011
European (non-Finnish)	0.0028%	35,759

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: EPAS1
Protein: p.Ser814=
Coding: c.2442G>A
MANE Select: NM_001430
dbSNP: rs4953362
Type: single nucleotide variant
Location: chr2:46382579 (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

Also linked: erythrocytosis, familial, 4

Similar variants

EPAS1 p.Ser814Leu Uncertain significance ★ ⚠ same residue
EPAS1 p.Ser814Trp Uncertain significance ★ ⚠ same residue
EPAS1 p.Ser814Pro Likely benign ★ same residue
EPAS1 p.Gly537Arg Pathogenic ★★ same condition
EPAS1 p.Met535Thr Pathogenic ★★ ⚠ same condition
EPAS1 c.-231C>G Uncertain significance ★★ same condition
EPAS1 p.Ala439Gly Uncertain significance ★★ ⚠ same condition
EPAS1 p.Ala463Thr 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-ser814 (accessed [today's date]).

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