Is EDARADD p.Cys100Arg (c.298T>C) pathogenic?

EDARADD p.Cys100Arg (c.298T>C) is classified Uncertain significance in EDARADD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely benign (0.2307); Very rare (popmax 0.00668%, afr); Associated with Inborn genetic diseases.

What condition is associated with EDARADD p.Cys100Arg (c.298T>C)?

EDARADD p.Cys100Arg (c.298T>C) is associated with Inborn genetic diseases (ClinVar).

How common is EDARADD p.Cys100Arg (c.298T>C) in the general population?

EDARADD p.Cys100Arg (c.298T>C) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about EDARADD p.Cys100Arg (c.298T>C)?

AlphaMissense predicts likely benign (score 0.2307) — an in-silico prediction, not a clinical call.

EDARADD p.Cys100Arg

c.298T>C · VCV4016153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2307 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2307	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -6.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 88 kb · p 0.0061 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,882 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000434% 7/1,613,980 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,976
Admixed American	0.00167%	59,978
European (non-Finnish)	8.47e-05%	1,180,044

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: EDARADD
Protein: p.Cys100Arg
Coding: c.298T>C
MANE Select: NM_145861
Type: single nucleotide variant
Location: chr1:236482299 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.81

Full EDARADD 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

EDARADD p.Arg170Gln Uncertain significance ★★ ⚠ same condition
EDARADD p.Gln8Glu Uncertain significance ★★ ⚠ same condition
EDARADD p.Gly74Arg Uncertain significance ★★ ⚠ same condition
EDARADD p.Arg108Gln Uncertain significance ★ ⚠ same condition
EDARADD p.Arg108Trp Uncertain significance ★ ⚠ same condition
EDARADD p.Arg206Trp Uncertain significance ★ ⚠ same condition
EDARADD p.Arg208His Uncertain significance ★ ⚠ same condition
EDARADD p.Asn117Asp 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/edaradd-p-cys100arg (accessed [today's date]).

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