Is EDA p.Arg357Gln (c.1070G>A) pathogenic?

EDA p.Arg357Gln (c.1070G>A) is classified Benign in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-29). AlphaMissense: likely benign (0.1888); Very rare (popmax 0.00297%, eas); Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Arg357Gln (c.1070G>A)?

EDA p.Arg357Gln (c.1070G>A) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Arg357Gln (c.1070G>A) in the general population?

EDA p.Arg357Gln (c.1070G>A) is very rare (popmax 0.00297%, eas) (gnomAD).

How is Hypohidrotic ectodermal dysplasia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about EDA p.Arg357Gln (c.1070G>A)?

AlphaMissense predicts likely benign (score 0.1888) — an in-silico prediction, not a clinical call.

EDA p.Arg357Gln

c.1070G>A · rs61747506 · VCV528362

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1888 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00297%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

X-linked hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
AlphaMissense	0.1888	likely benign
REVEL	0.54	indeterminate
SaProt	LLR -7.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 4.7, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00297% East Asian · 1/33,661 alleles

Filtering AF 0.00101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000798%

Overall 0.00514% 62/1,206,739 alleles · very rare exomes 56/1,098,216 · genomes 6/108,523 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.173%	579
Remaining individualsnot grpmax-eligible	0.0126%	7,923
East Asiangrpmax	0.00297%	33,661
African / African-American	0.00178%	56,119
South Asian	0.00177%	56,544
European (non-Finnish)	0.00168%	59,635

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EDA
Protein: p.Arg357Gln
Coding: c.1070G>A
MANE Select: NM_001399
dbSNP: rs61747506
Type: single nucleotide variant
Location: chrX:70035503 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 357: a UniProt-annotated variant site (in xhed); the thd domain

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

Disease context

X-linked hypohidrotic ectodermal dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hypohidrotic ectodermal dysplasia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

EDA p.Arg357Trp Pathogenic/Likely pathogenic ★★ same residue
EDA p.Arg357= Likely benign ★ same residue
EDA p.Arg357Gly Uncertain significance ★ ⚠ same residue
EDA p.Arg357Pro Uncertain significance ★ ⚠ same residue
EDA c.526+5G>T Likely pathogenic ★★ same condition
EDA c.527-2A>G Pathogenic/Likely pathogenic ★★ same condition
EDA c.706+1G>A Pathogenic/Likely pathogenic ★★ same condition
EDA c.707-13T>G 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/eda-p-arg357gln (accessed [today's date]).

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