Is ROGDI p.Leu206= (c.616C>T) pathogenic?

ROGDI p.Leu206= (c.616C>T) is classified Likely benign in ROGDI (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-04). Absent from gnomAD v4.1; Associated with amelocerebrohypohidrotic syndrome.

What condition is associated with ROGDI p.Leu206= (c.616C>T)?

ROGDI p.Leu206= (c.616C>T) is associated with amelocerebrohypohidrotic syndrome (ClinVar).

How common is ROGDI p.Leu206= (c.616C>T) in the general population?

ROGDI p.Leu206= (c.616C>T) is absent from gnomAD v4.1 (gnomAD).

ROGDI p.Leu206=

c.616C>T · rs1384897869 · VCV2106795

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

amelocerebrohypohidrotic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.66 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.6	GERP 0.55, phastCons 1
Overall
CADD	10.13	PHRED · no single calibrated threshold — expert panels disagree

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.Leu206=
Coding: c.616C>T
MANE Select: NM_024589
dbSNP: rs1384897869
Type: single nucleotide variant
Location: chr16:4798100 (GRCh38)
Gene constraint: LOEUF 1.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.59 · 2 PDB
Residue 206: a β-strand; 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.Leu206Val Uncertain significance ★ ⚠ 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-leu206 (accessed [today's date]).

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