Is EPAS1 p.Ala100= (c.300C>T) pathogenic?

EPAS1 p.Ala100= (c.300C>T) is classified Likely benign in EPAS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-08). Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with EPAS1 p.Ala100= (c.300C>T)?

EPAS1 p.Ala100= (c.300C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EPAS1 p.Ala100= (c.300C>T) in the general population?

EPAS1 p.Ala100= (c.300C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

EPAS1 p.Ala100=

c.300C>T · rs781580686 · VCV1798786

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 -12	GERP -4.1
Overall
CADD	6.213	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,062 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000958% 14/1,461,508 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,531
European (non-Finnish)	0.00102%	98,306

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.Ala100=
Coding: c.300C>T
MANE Select: NM_001430
dbSNP: rs781580686
Type: single nucleotide variant
Location: chr2:46356233 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.41 · 43 PDB
Residue 100: the pas 1 domain

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.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
EPAS1 p.Ala94Val Uncertain significance ★★ same condition
EPAS1 p.Arg181Cys 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-ala100 (accessed [today's date]).

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