Is EDA p.Pro200Gln (c.599C>A) pathogenic?

EDA p.Pro200Gln (c.599C>A) is classified Uncertain significance in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2011-09-20). AlphaMissense: likely pathogenic (0.692); Absent from gnomAD v4.1.

How common is EDA p.Pro200Gln (c.599C>A) in the general population?

EDA p.Pro200Gln (c.599C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDA p.Pro200Gln (c.599C>A)?

AlphaMissense predicts likely pathogenic (score 0.692) — an in-silico prediction, not a clinical call.

EDA p.Pro200Gln

c.599C>A · rs397516669 · VCV44201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.692 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,180,974)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.692	likely pathogenic
REVEL	0.494	indeterminate
SaProt	LLR -8.05	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 3.9, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	24.7	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

No allele count reported in gnomAD v4.1 (AN 1,180,974). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EDA
Protein: p.Pro200Gln
Coding: c.599C>A
MANE Select: NM_001399
dbSNP: rs397516669
Type: single nucleotide variant
Location: chrX:70027929 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 200: the collagen-like domain; a UniProt-annotated variant site (in xhed; uncertain significance); the 'disordered' region

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

Similar variants

EDA p.Pro200Leu Pathogenic same residue
EDA p.Pro200fs Pathogenic ★ same residue
EDA c.526+2T>C Pathogenic/Likely pathogenic ★★ same type
EDA c.526+5G>T Likely pathogenic ★★ same type
EDA c.527-2A>G Pathogenic/Likely pathogenic ★★ same type
EDA c.706+1G>A Pathogenic/Likely pathogenic ★★ same type
EDA c.707-13T>G Pathogenic ★★ same type
EDA c.742-2A>G Pathogenic/Likely pathogenic ★★ same type

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-pro200gln (accessed [today's date]).

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