Is EDAR p.Arg358Ter (c.1072C>T) pathogenic?

EDAR p.Arg358Ter (c.1072C>T) is classified Pathogenic in EDAR (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-06-05). Very rare (popmax 8.47e-05%, nfe); Associated with EDAR-related disorder.

How common is EDAR p.Arg358Ter (c.1072C>T) in the general population?

EDAR p.Arg358Ter (c.1072C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

EDAR p.Arg358Ter

Q: What condition is associated with EDAR p.Arg358Ter (c.1072C>T)?

EDAR p.Arg358Ter (c.1072C>T) is associated with EDAR-related disorder, ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, autosomal recessive hypohidrotic ectodermal dysplasia (ClinVar).

c.1072C>T · rs121908452 · VCV5852

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

EDAR-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.1, phastCons 1
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.84e-05% 1/1,461,552 alleles · very rare

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: EDAR
Protein: p.Arg358Ter
Coding: c.1072C>T
MANE Select: NM_022336
dbSNP: rs121908452
Type: single nucleotide variant
Location: chr2:108897182 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 358: a UniProt-annotated variant site (in ectd10b); the death domain

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

Disease context

EDAR-related disorder

Also linked: ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant autosomal recessive hypohidrotic ectodermal dysplasia

Similar variants

EDAR p.Ala26Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
EDAR p.Arg25Ter Pathogenic/Likely pathogenic ★★ same condition
EDAR p.Arg420Gln Pathogenic/Likely pathogenic ★★ same condition
EDAR p.Arg89His Pathogenic/Likely pathogenic ★★ ⚠ same condition
EDAR p.Arg98Trp Pathogenic/Likely pathogenic ★★ same condition
EDAR p.Cys301Ter Pathogenic ★★ same condition
EDAR p.Cys428Arg Pathogenic/Likely pathogenic ★★ same condition
EDAR p.Gly382Ser Pathogenic ★★ 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/edar-p-arg358ter (accessed [today's date]).

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