Is ROGDI p.Pro286Ala (c.856C>G) pathogenic?

ROGDI p.Pro286Ala (c.856C>G) is classified Uncertain significance in ROGDI (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-18). AlphaMissense: likely benign (0.1144); Absent from gnomAD v4.1; Associated with amelocerebrohypohidrotic syndrome.

What condition is associated with ROGDI p.Pro286Ala (c.856C>G)?

ROGDI p.Pro286Ala (c.856C>G) is associated with amelocerebrohypohidrotic syndrome (ClinVar).

How common is ROGDI p.Pro286Ala (c.856C>G) in the general population?

ROGDI p.Pro286Ala (c.856C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ROGDI p.Pro286Ala (c.856C>G)?

AlphaMissense predicts likely benign (score 0.1144) — an in-silico prediction, not a clinical call.

ROGDI p.Pro286Ala

c.856C>G · rs2082664303 · VCV1034680

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1144 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

amelocerebrohypohidrotic syndrome

Computational evidence

Protein change
AlphaMissense	0.1144	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -6.49	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 -1.7, phastCons 1
Regional constraint	o/e 1.35	unconstrained · MANE · 5,108 bp · p 7.6e-12 · regional, not allelic
Overall
CADD	18.84	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ROGDI
Protein: p.Pro286Ala
Coding: c.856C>G
MANE Select: NM_024589
dbSNP: rs2082664303
Type: single nucleotide variant
Location: chr16:4797468 (GRCh38)
Gene constraint: LOEUF 1.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.59 · 2 PDB
Residue 286: a UniProt-annotated variant site (in ktzs; uncertain significance); a UniProt-annotated variant site (in ktzs)

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

Disease context

amelocerebrohypohidrotic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ROGDI p.Pro286= Likely benign ★ same residue
ROGDI c.117+1G>A Pathogenic/Likely pathogenic ★★ same condition
ROGDI c.46-2A>G Likely pathogenic ★★ same condition
ROGDI c.531+5G>C Likely pathogenic ★★ same condition
ROGDI c.645+2T>A Likely pathogenic ★★ same condition
ROGDI p.Arg157Ter Pathogenic ★★ same condition
ROGDI p.Gln112Ter Pathogenic/Likely pathogenic ★★ same condition
ROGDI p.Gln114Ter Pathogenic/Likely 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/rogdi-p-pro286ala (accessed [today's date]).

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