Is EDNRA p.Ala8= (c.24A>G) pathogenic?

EDNRA p.Ala8= (c.24A>G) is classified Benign/Likely benign in EDNRA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-15). Rare (popmax 0.297%, afr); Associated with mandibulofacial dysostosis with alopecia.

What condition is associated with EDNRA p.Ala8= (c.24A>G)?

EDNRA p.Ala8= (c.24A>G) is associated with mandibulofacial dysostosis with alopecia, migraine with or without aura, susceptibility to, 1 (ClinVar).

How common is EDNRA p.Ala8= (c.24A>G) in the general population?

EDNRA p.Ala8= (c.24A>G) is rare (popmax 0.297%, afr) (gnomAD).

EDNRA p.Ala8=

c.24A>G · rs146092355 · VCV1166335

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.297%, afr)

Conditions

mandibulofacial dysostosis with alopecia

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 -0.27	GERP -5.5
Overall
CADD	7.603	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.297% African / African-American · 223/74,976 alleles

Filtering AF 0.265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.253%

Overall 0.0151% 243/1,609,230 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.297%	336
Remaining individualsnot grpmax-eligible	0.0176%	5,667
Middle Eastern	0.0166%	6,034
Admixed American	0.01%	9,975
European (non-Finnish)	0.00017%	588,356

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: EDNRA
Protein: p.Ala8=
Coding: c.24A>G
MANE Select: NM_001957
dbSNP: rs146092355
Type: single nucleotide variant
Location: chr4:147485705 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.45 · 5 PDB

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

Disease context

mandibulofacial dysostosis with alopecia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: migraine with or without aura, susceptibility to, 1

Similar variants

EDNRA p.Ile82Leu Uncertain significance ★★ ⚠ same condition
EDNRA c.1034+19G>A Benign/Likely benign ★★ same condition
EDNRA c.549-10T>C Likely benign ★★ same condition
EDNRA p.Glu335= Benign ★★ same condition
EDNRA p.His323= Benign ★★ same condition
EDNRA p.Leu118= Likely benign ★★ same condition
EDNRA p.Ser382= Benign/Likely benign ★★ same condition
EDNRA p.Tyr370= Benign/Likely benign ★★ 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/ednra-p-ala8 (accessed [today's date]).

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