Is EPAS1 p.Ala472= (c.1416C>T) pathogenic?

EPAS1 p.Ala472= (c.1416C>T) is classified Likely benign in EPAS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-30). Very rare (popmax 0.00224%, eas); Associated with Inborn genetic diseases.

What condition is associated with EPAS1 p.Ala472= (c.1416C>T)?

EPAS1 p.Ala472= (c.1416C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EPAS1 p.Ala472= (c.1416C>T) in the general population?

EPAS1 p.Ala472= (c.1416C>T) is very rare (popmax 0.00224%, eas) (gnomAD).

EPAS1 p.Ala472=

c.1416C>T · rs185487482 · VCV1772136

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

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 0.26	GERP 1.4, phastCons 0.68
Overall
CADD	8.856	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,668 alleles

Overall 0.000124% 2/1,606,762 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,668
African / African-American	0.00134%	74,900

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.Ala472=
Coding: c.1416C>T
MANE Select: NM_001430
dbSNP: rs185487482
Type: single nucleotide variant
Location: chr2:46378060 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.41 · 43 PDB
Residue 472: the 'disordered' region

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-ala472 (accessed [today's date]).

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