Is ROGDI p.Phe100= (c.300C>T) pathogenic?

ROGDI p.Phe100= (c.300C>T) is classified Likely benign in ROGDI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). Very rare (popmax 0.00271%, afr); Associated with amelocerebrohypohidrotic syndrome.

What condition is associated with ROGDI p.Phe100= (c.300C>T)?

ROGDI p.Phe100= (c.300C>T) is associated with amelocerebrohypohidrotic syndrome (ClinVar).

How common is ROGDI p.Phe100= (c.300C>T) in the general population?

ROGDI p.Phe100= (c.300C>T) is very rare (popmax 0.00271%, afr) (gnomAD).

ROGDI p.Phe100=

c.300C>T · rs371657994 · VCV2048088

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00271%, afr)

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 -4.2	GERP -2.7
Overall
CADD	1.483	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% African / African-American · 2/73,836 alleles

Filtering AF 0.000629% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000484%

Overall 0.00102% 16/1,564,726 alleles · very rare exomes 15/1,412,504 · genomes 1/152,222 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00271%	36,918
South Asian	0.00118%	85,082
European (non-Finnish)	0.00113%	88,766

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: ROGDI
Protein: p.Phe100=
Coding: c.300C>T
MANE Select: NM_024589
dbSNP: rs371657994
Type: single nucleotide variant
Location: chr16:4800534 (GRCh38)
Gene constraint: LOEUF 1.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.59 · 2 PDB
Residue 100: a β-strand

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.Phe100Leu 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-phe100 (accessed [today's date]).

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