Is ROGDI p.Ala6= (c.18A>G) pathogenic?

ROGDI p.Ala6= (c.18A>G) is classified Likely benign in ROGDI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). No allele count reported in gnomAD v4.1 (AN 1,295,166); Associated with amelocerebrohypohidrotic syndrome.

What condition is associated with ROGDI p.Ala6= (c.18A>G)?

ROGDI p.Ala6= (c.18A>G) is associated with amelocerebrohypohidrotic syndrome (ClinVar).

How common is ROGDI p.Ala6= (c.18A>G) in the general population?

ROGDI p.Ala6= (c.18A>G) is no allele count reported in gnomAD v4.1 (AN 1,295,166) (gnomAD).

ROGDI p.Ala6=

c.18A>G · rs2505737122 · VCV2787794

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,295,166)

Conditions

amelocerebrohypohidrotic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -0.86, phastCons 0.87
Overall
CADD	11.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,295,166). 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: ROGDI
Protein: p.Ala6=
Coding: c.18A>G
MANE Select: NM_024589
dbSNP: rs2505737122
Type: single nucleotide variant
Location: chr16:4802554 (GRCh38)
Gene constraint: LOEUF 1.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.59 · 2 PDB
Residue 6: an α-helix

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.Ala6Ser 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-ala6 (accessed [today's date]).

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